User login
Head, neck cancer radiotherapy regimen saves time when resources limited
SAN DIEGO – In low- and middle-income countries with high incidence and mortality from head and neck cancer, resources remain limited. Patients often can’t travel far for treatment or afford to stay near a treatment center for the length of time required for conventionally fractionated radiotherapy.
in these settings.
The phase 3 randomized HYPNO trial, conducted in 10 low- and middle-income countries, revealed that the hypofractionated regimen shortened total treatment time by a median of 11.5 days and was noninferior to conventional fractionation for tumor control and safety.
The primary trial results were presented by Søren Bentzen, PhD, DMSc, at the annual meeting of the American Society for Radiation Oncology.
“It was Usain Bolt who said, ‘I train for 4 years to run 9 seconds,’ and that was the feeling that I had when we did the noninferiority test,” said Dr. Bentzen, from the University of Maryland School of Medicine in Baltimore. “We had not looked at the data while the data were being accumulated, and guess what? It actually turned out that we had noninferiority with respect to both locoregional control and the late effects.”
In the HYPNO trial, Dr. Bentzen and colleagues wanted to determine whether a streamlined approach to the treatment of patients in low- and middle-income countries could improve access to care and still achieve strong outcomes.
The investigators used mathematical modeling to devise a strategy to reduce the number of fractions and put this hypothesis to the test in a pragmatic trial.
Patients from Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines were enrolled. After stratification by performance status, tumor subsite, institution, and previous treatment with chemotherapy, the 792 patients in the trial were randomly assigned in a 1:1 ratio to receive either 66 Gy in 33 fractions 6 days each week over 5.5 weeks, or 55 Gy in 20 fractions 5 days per week over 4 weeks. In both groups, weekly cisplatin was optional.
Compliance with the regimens was high in both arms, with 95% of patients assigned to conventional fractionation and 99% assigned to hypofractionation receiving the total planned doses.
At 3 years’ follow-up, the rates of locoregional control were 50.7% in the hypofractionation arm and 51.2% in the conventional fractionation arm (P = .40). No significant differences between the groups have emerged over 5 years, Dr. Bentzen said.
Rates of late toxicities of grade 3 or greater at 3 years’ follow-up were similar between the groups, at 18.8% in the hypofractionation arm and 20.2% in the conventional fractionation arm (P = .68).
Three-year overall survival rates also did not differ between the groups – 54.1% in the hypofractionation arm vs. 55.5% in the conventional arm (P = .62) – nor did rates of progression-free survival – 44.0% vs. 45.3%.
“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden especially in lower- and middle-income countries,” Dr. Bentzen said in a press release. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”
Beth Beadle, MD, PhD, the invited discussant at a media briefing where Dr. Bentzen summarized the findings, said, “I think this trial is going to change practice in low- and middle-income countries and will improve access to care.”
Although the approach used in the HYPNO trial will likely allow more patients to receive treatment and will save lives in countries with limited resources, the strategy likely won’t apply to U.S. practice, noted Dr. Beadle, a professor of radiation oncology at Stanford University, California.
“The one thing I do caution, and that Dr. Bentzen brought up, is that this is a very different population than the one that we see in the United States now,” Dr. Beadle said. “In fact, it’s very challenging to find a similar patient population to even serve as a comparison in the modern era and modern techniques.”
The HYPNO trial was sponsored by the International Atomic Energy Agency. Dr. Bentzen and Dr. Beadle have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – In low- and middle-income countries with high incidence and mortality from head and neck cancer, resources remain limited. Patients often can’t travel far for treatment or afford to stay near a treatment center for the length of time required for conventionally fractionated radiotherapy.
in these settings.
The phase 3 randomized HYPNO trial, conducted in 10 low- and middle-income countries, revealed that the hypofractionated regimen shortened total treatment time by a median of 11.5 days and was noninferior to conventional fractionation for tumor control and safety.
The primary trial results were presented by Søren Bentzen, PhD, DMSc, at the annual meeting of the American Society for Radiation Oncology.
“It was Usain Bolt who said, ‘I train for 4 years to run 9 seconds,’ and that was the feeling that I had when we did the noninferiority test,” said Dr. Bentzen, from the University of Maryland School of Medicine in Baltimore. “We had not looked at the data while the data were being accumulated, and guess what? It actually turned out that we had noninferiority with respect to both locoregional control and the late effects.”
In the HYPNO trial, Dr. Bentzen and colleagues wanted to determine whether a streamlined approach to the treatment of patients in low- and middle-income countries could improve access to care and still achieve strong outcomes.
The investigators used mathematical modeling to devise a strategy to reduce the number of fractions and put this hypothesis to the test in a pragmatic trial.
Patients from Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines were enrolled. After stratification by performance status, tumor subsite, institution, and previous treatment with chemotherapy, the 792 patients in the trial were randomly assigned in a 1:1 ratio to receive either 66 Gy in 33 fractions 6 days each week over 5.5 weeks, or 55 Gy in 20 fractions 5 days per week over 4 weeks. In both groups, weekly cisplatin was optional.
Compliance with the regimens was high in both arms, with 95% of patients assigned to conventional fractionation and 99% assigned to hypofractionation receiving the total planned doses.
At 3 years’ follow-up, the rates of locoregional control were 50.7% in the hypofractionation arm and 51.2% in the conventional fractionation arm (P = .40). No significant differences between the groups have emerged over 5 years, Dr. Bentzen said.
Rates of late toxicities of grade 3 or greater at 3 years’ follow-up were similar between the groups, at 18.8% in the hypofractionation arm and 20.2% in the conventional fractionation arm (P = .68).
Three-year overall survival rates also did not differ between the groups – 54.1% in the hypofractionation arm vs. 55.5% in the conventional arm (P = .62) – nor did rates of progression-free survival – 44.0% vs. 45.3%.
“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden especially in lower- and middle-income countries,” Dr. Bentzen said in a press release. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”
Beth Beadle, MD, PhD, the invited discussant at a media briefing where Dr. Bentzen summarized the findings, said, “I think this trial is going to change practice in low- and middle-income countries and will improve access to care.”
Although the approach used in the HYPNO trial will likely allow more patients to receive treatment and will save lives in countries with limited resources, the strategy likely won’t apply to U.S. practice, noted Dr. Beadle, a professor of radiation oncology at Stanford University, California.
“The one thing I do caution, and that Dr. Bentzen brought up, is that this is a very different population than the one that we see in the United States now,” Dr. Beadle said. “In fact, it’s very challenging to find a similar patient population to even serve as a comparison in the modern era and modern techniques.”
The HYPNO trial was sponsored by the International Atomic Energy Agency. Dr. Bentzen and Dr. Beadle have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – In low- and middle-income countries with high incidence and mortality from head and neck cancer, resources remain limited. Patients often can’t travel far for treatment or afford to stay near a treatment center for the length of time required for conventionally fractionated radiotherapy.
in these settings.
The phase 3 randomized HYPNO trial, conducted in 10 low- and middle-income countries, revealed that the hypofractionated regimen shortened total treatment time by a median of 11.5 days and was noninferior to conventional fractionation for tumor control and safety.
The primary trial results were presented by Søren Bentzen, PhD, DMSc, at the annual meeting of the American Society for Radiation Oncology.
“It was Usain Bolt who said, ‘I train for 4 years to run 9 seconds,’ and that was the feeling that I had when we did the noninferiority test,” said Dr. Bentzen, from the University of Maryland School of Medicine in Baltimore. “We had not looked at the data while the data were being accumulated, and guess what? It actually turned out that we had noninferiority with respect to both locoregional control and the late effects.”
In the HYPNO trial, Dr. Bentzen and colleagues wanted to determine whether a streamlined approach to the treatment of patients in low- and middle-income countries could improve access to care and still achieve strong outcomes.
The investigators used mathematical modeling to devise a strategy to reduce the number of fractions and put this hypothesis to the test in a pragmatic trial.
Patients from Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines were enrolled. After stratification by performance status, tumor subsite, institution, and previous treatment with chemotherapy, the 792 patients in the trial were randomly assigned in a 1:1 ratio to receive either 66 Gy in 33 fractions 6 days each week over 5.5 weeks, or 55 Gy in 20 fractions 5 days per week over 4 weeks. In both groups, weekly cisplatin was optional.
Compliance with the regimens was high in both arms, with 95% of patients assigned to conventional fractionation and 99% assigned to hypofractionation receiving the total planned doses.
At 3 years’ follow-up, the rates of locoregional control were 50.7% in the hypofractionation arm and 51.2% in the conventional fractionation arm (P = .40). No significant differences between the groups have emerged over 5 years, Dr. Bentzen said.
Rates of late toxicities of grade 3 or greater at 3 years’ follow-up were similar between the groups, at 18.8% in the hypofractionation arm and 20.2% in the conventional fractionation arm (P = .68).
Three-year overall survival rates also did not differ between the groups – 54.1% in the hypofractionation arm vs. 55.5% in the conventional arm (P = .62) – nor did rates of progression-free survival – 44.0% vs. 45.3%.
“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden especially in lower- and middle-income countries,” Dr. Bentzen said in a press release. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”
Beth Beadle, MD, PhD, the invited discussant at a media briefing where Dr. Bentzen summarized the findings, said, “I think this trial is going to change practice in low- and middle-income countries and will improve access to care.”
Although the approach used in the HYPNO trial will likely allow more patients to receive treatment and will save lives in countries with limited resources, the strategy likely won’t apply to U.S. practice, noted Dr. Beadle, a professor of radiation oncology at Stanford University, California.
“The one thing I do caution, and that Dr. Bentzen brought up, is that this is a very different population than the one that we see in the United States now,” Dr. Beadle said. “In fact, it’s very challenging to find a similar patient population to even serve as a comparison in the modern era and modern techniques.”
The HYPNO trial was sponsored by the International Atomic Energy Agency. Dr. Bentzen and Dr. Beadle have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASTRO 2023
Reducing cognitive impairment from SCLC brain metastases
For patients with up to 10 brain metastases from small cell lung cancer (SCLC), stereotactic radiosurgery was associated with less cognitive impairment than whole-brain radiation therapy (WBRT) without compromising overall survival, results of the randomized ENCEPHALON (ARO 2018-9) trial suggest.
Among 56 patients with one to 10 SCLC brain metastases, 24% of those who received WBRT demonstrated significant declines in memory function 3 months after treatment, compared with 7% of patients whose metastases were treated with stereotactic radiosurgery alone. Preliminary data showed no significant differences in overall survival between the treatment groups at 6 months of follow-up, Denise Bernhardt, MD, from the Technical University of Munich, reported at the American Society of Radiation Oncology (ASTRO) annual meeting.
“We propose stereotactic radiosurgery should be an option for patients with up to 10 brain metastases in small cell lung cancer,” Dr. Bernhardt said during her presentation.
Vinai Gondi, MD, who was not involved in the study, said that the primary results from the trial – while limited by the study’s small size and missing data – are notable.
Patients with brain metastases from most cancer types typically receive stereotactic radiosurgery but WBRT has remained the standard of care to control brain metastases among patients with SCLC.
“This is the first prospective trial of radiosurgery versus whole-brain radiotherapy for small cell lung cancer brain metastases, and it’s important to recognize how important this is,” said Dr. Gondi, director of Radiation Oncology and codirector of the Brain Tumor Center at Northwestern Medicine Cancer Center, Warrenville, Ill.
Prior trials that have asked the same question did not include SCLC because many of those patients received prophylactic cranial irradiation, Dr. Gondi explained. Prophylactic cranial irradiation, however, has been on the decline among patients with brain metastases from SCLC, following a study from Japan showing no difference in survival among those who received the therapy and those followed with observation as well as evidence demonstrating significant toxicities associated with the technique.
Now “with the declining use of prophylactic cranial irradiation, the emergence of brain metastases is increasing significantly in volume in the small cell lung cancer population,” said Dr. Gondi, who is principal investigator on a phase 3 trial exploring stereotactic radiosurgery versus WBRT in a similar patient population.
In a previous retrospective trial), Dr. Bernhardt and colleagues found that first-line stereotactic radiosurgery did not compromise survival, compared with WBRT, but patients receiving stereotactic radiosurgery did have a higher risk for intracranial failure.
In the current study, the investigators compared the neurocognitive responses in patients with brain metastases from SCLC treated with stereotactic radiosurgery or WBRT.
Enrolled patients had histologically confirmed extensive disease with up to 10 metastatic brain lesions and had not previously received either therapeutic or prophylactic brain irradiation. After stratifying patients by synchronous versus metachronous disease, 56 patients were randomly assigned to either WBRT, at a total dose of 30 Gy delivered in 10 fractions, or to stereotactic radiosurgery with 20 Gy, 18 Gy, or fractionated stereotactic radiosurgery with 30 Gy in 5 Gy fractions for lesions larger than 3 cm.
The primary endpoint was neurocognition after radiation therapy as defined by a decline from baseline of at least five points on the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall subscale at 3 months. Secondary endpoints included survival outcomes, additional neurocognitive assessments of motor skills, executive function, attention, memory, and processing as well as quality-of-life measures.
The investigators expected a high rate of study dropout and planned their statistical analysis accordingly, using a method for estimating the likely values of missing data based on observed data.
Among 26 patients who eventually underwent stereotactic radiosurgery, 18 did not meet the primary endpoint and 2 (7%) demonstrated declines on the HVLT-R subscale of 5 or more points. Data for the remaining 6 patients were missing.
Among the 25 who underwent WBRT, 13 did not meet the primary endpoint and 6 (24%) demonstrated declines of at least 5 points. Data for 6 of the remaining patients were missing.
Although more patients in the WBRT arm had significant declines in neurocognitive function, the difference between the groups was not significant, due to the high proportion of study dropouts – approximately one-fourth of patients in each arm. But the analysis suggested that the neuroprotective effect of stereotactic radiosurgery was notable, Dr. Bernhardt said.
At 6 months, the team also found no significant difference in the survival probability between the treatment groups (P = .36). The median time to death was 124 days among patients who received stereotactic radiosurgery and 131 days among patients who received WBRT.
Dr. Gondi said the data from ENCEPHALON, while promising, need to be carefully scrutinized because of the small sample sizes and the possibility for unintended bias.
ARO 2018-9 is an investigator-initiated trial funded by Accuray. Dr. Bernhardt disclosed consulting actives, fees, travel expenses, and research funding from Accuray and others. Dr. Gondi disclosed honoraria from UpToDate.
A version of this article appeared on Medscape.com.
For patients with up to 10 brain metastases from small cell lung cancer (SCLC), stereotactic radiosurgery was associated with less cognitive impairment than whole-brain radiation therapy (WBRT) without compromising overall survival, results of the randomized ENCEPHALON (ARO 2018-9) trial suggest.
Among 56 patients with one to 10 SCLC brain metastases, 24% of those who received WBRT demonstrated significant declines in memory function 3 months after treatment, compared with 7% of patients whose metastases were treated with stereotactic radiosurgery alone. Preliminary data showed no significant differences in overall survival between the treatment groups at 6 months of follow-up, Denise Bernhardt, MD, from the Technical University of Munich, reported at the American Society of Radiation Oncology (ASTRO) annual meeting.
“We propose stereotactic radiosurgery should be an option for patients with up to 10 brain metastases in small cell lung cancer,” Dr. Bernhardt said during her presentation.
Vinai Gondi, MD, who was not involved in the study, said that the primary results from the trial – while limited by the study’s small size and missing data – are notable.
Patients with brain metastases from most cancer types typically receive stereotactic radiosurgery but WBRT has remained the standard of care to control brain metastases among patients with SCLC.
“This is the first prospective trial of radiosurgery versus whole-brain radiotherapy for small cell lung cancer brain metastases, and it’s important to recognize how important this is,” said Dr. Gondi, director of Radiation Oncology and codirector of the Brain Tumor Center at Northwestern Medicine Cancer Center, Warrenville, Ill.
Prior trials that have asked the same question did not include SCLC because many of those patients received prophylactic cranial irradiation, Dr. Gondi explained. Prophylactic cranial irradiation, however, has been on the decline among patients with brain metastases from SCLC, following a study from Japan showing no difference in survival among those who received the therapy and those followed with observation as well as evidence demonstrating significant toxicities associated with the technique.
Now “with the declining use of prophylactic cranial irradiation, the emergence of brain metastases is increasing significantly in volume in the small cell lung cancer population,” said Dr. Gondi, who is principal investigator on a phase 3 trial exploring stereotactic radiosurgery versus WBRT in a similar patient population.
In a previous retrospective trial), Dr. Bernhardt and colleagues found that first-line stereotactic radiosurgery did not compromise survival, compared with WBRT, but patients receiving stereotactic radiosurgery did have a higher risk for intracranial failure.
In the current study, the investigators compared the neurocognitive responses in patients with brain metastases from SCLC treated with stereotactic radiosurgery or WBRT.
Enrolled patients had histologically confirmed extensive disease with up to 10 metastatic brain lesions and had not previously received either therapeutic or prophylactic brain irradiation. After stratifying patients by synchronous versus metachronous disease, 56 patients were randomly assigned to either WBRT, at a total dose of 30 Gy delivered in 10 fractions, or to stereotactic radiosurgery with 20 Gy, 18 Gy, or fractionated stereotactic radiosurgery with 30 Gy in 5 Gy fractions for lesions larger than 3 cm.
The primary endpoint was neurocognition after radiation therapy as defined by a decline from baseline of at least five points on the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall subscale at 3 months. Secondary endpoints included survival outcomes, additional neurocognitive assessments of motor skills, executive function, attention, memory, and processing as well as quality-of-life measures.
The investigators expected a high rate of study dropout and planned their statistical analysis accordingly, using a method for estimating the likely values of missing data based on observed data.
Among 26 patients who eventually underwent stereotactic radiosurgery, 18 did not meet the primary endpoint and 2 (7%) demonstrated declines on the HVLT-R subscale of 5 or more points. Data for the remaining 6 patients were missing.
Among the 25 who underwent WBRT, 13 did not meet the primary endpoint and 6 (24%) demonstrated declines of at least 5 points. Data for 6 of the remaining patients were missing.
Although more patients in the WBRT arm had significant declines in neurocognitive function, the difference between the groups was not significant, due to the high proportion of study dropouts – approximately one-fourth of patients in each arm. But the analysis suggested that the neuroprotective effect of stereotactic radiosurgery was notable, Dr. Bernhardt said.
At 6 months, the team also found no significant difference in the survival probability between the treatment groups (P = .36). The median time to death was 124 days among patients who received stereotactic radiosurgery and 131 days among patients who received WBRT.
Dr. Gondi said the data from ENCEPHALON, while promising, need to be carefully scrutinized because of the small sample sizes and the possibility for unintended bias.
ARO 2018-9 is an investigator-initiated trial funded by Accuray. Dr. Bernhardt disclosed consulting actives, fees, travel expenses, and research funding from Accuray and others. Dr. Gondi disclosed honoraria from UpToDate.
A version of this article appeared on Medscape.com.
For patients with up to 10 brain metastases from small cell lung cancer (SCLC), stereotactic radiosurgery was associated with less cognitive impairment than whole-brain radiation therapy (WBRT) without compromising overall survival, results of the randomized ENCEPHALON (ARO 2018-9) trial suggest.
Among 56 patients with one to 10 SCLC brain metastases, 24% of those who received WBRT demonstrated significant declines in memory function 3 months after treatment, compared with 7% of patients whose metastases were treated with stereotactic radiosurgery alone. Preliminary data showed no significant differences in overall survival between the treatment groups at 6 months of follow-up, Denise Bernhardt, MD, from the Technical University of Munich, reported at the American Society of Radiation Oncology (ASTRO) annual meeting.
“We propose stereotactic radiosurgery should be an option for patients with up to 10 brain metastases in small cell lung cancer,” Dr. Bernhardt said during her presentation.
Vinai Gondi, MD, who was not involved in the study, said that the primary results from the trial – while limited by the study’s small size and missing data – are notable.
Patients with brain metastases from most cancer types typically receive stereotactic radiosurgery but WBRT has remained the standard of care to control brain metastases among patients with SCLC.
“This is the first prospective trial of radiosurgery versus whole-brain radiotherapy for small cell lung cancer brain metastases, and it’s important to recognize how important this is,” said Dr. Gondi, director of Radiation Oncology and codirector of the Brain Tumor Center at Northwestern Medicine Cancer Center, Warrenville, Ill.
Prior trials that have asked the same question did not include SCLC because many of those patients received prophylactic cranial irradiation, Dr. Gondi explained. Prophylactic cranial irradiation, however, has been on the decline among patients with brain metastases from SCLC, following a study from Japan showing no difference in survival among those who received the therapy and those followed with observation as well as evidence demonstrating significant toxicities associated with the technique.
Now “with the declining use of prophylactic cranial irradiation, the emergence of brain metastases is increasing significantly in volume in the small cell lung cancer population,” said Dr. Gondi, who is principal investigator on a phase 3 trial exploring stereotactic radiosurgery versus WBRT in a similar patient population.
In a previous retrospective trial), Dr. Bernhardt and colleagues found that first-line stereotactic radiosurgery did not compromise survival, compared with WBRT, but patients receiving stereotactic radiosurgery did have a higher risk for intracranial failure.
In the current study, the investigators compared the neurocognitive responses in patients with brain metastases from SCLC treated with stereotactic radiosurgery or WBRT.
Enrolled patients had histologically confirmed extensive disease with up to 10 metastatic brain lesions and had not previously received either therapeutic or prophylactic brain irradiation. After stratifying patients by synchronous versus metachronous disease, 56 patients were randomly assigned to either WBRT, at a total dose of 30 Gy delivered in 10 fractions, or to stereotactic radiosurgery with 20 Gy, 18 Gy, or fractionated stereotactic radiosurgery with 30 Gy in 5 Gy fractions for lesions larger than 3 cm.
The primary endpoint was neurocognition after radiation therapy as defined by a decline from baseline of at least five points on the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall subscale at 3 months. Secondary endpoints included survival outcomes, additional neurocognitive assessments of motor skills, executive function, attention, memory, and processing as well as quality-of-life measures.
The investigators expected a high rate of study dropout and planned their statistical analysis accordingly, using a method for estimating the likely values of missing data based on observed data.
Among 26 patients who eventually underwent stereotactic radiosurgery, 18 did not meet the primary endpoint and 2 (7%) demonstrated declines on the HVLT-R subscale of 5 or more points. Data for the remaining 6 patients were missing.
Among the 25 who underwent WBRT, 13 did not meet the primary endpoint and 6 (24%) demonstrated declines of at least 5 points. Data for 6 of the remaining patients were missing.
Although more patients in the WBRT arm had significant declines in neurocognitive function, the difference between the groups was not significant, due to the high proportion of study dropouts – approximately one-fourth of patients in each arm. But the analysis suggested that the neuroprotective effect of stereotactic radiosurgery was notable, Dr. Bernhardt said.
At 6 months, the team also found no significant difference in the survival probability between the treatment groups (P = .36). The median time to death was 124 days among patients who received stereotactic radiosurgery and 131 days among patients who received WBRT.
Dr. Gondi said the data from ENCEPHALON, while promising, need to be carefully scrutinized because of the small sample sizes and the possibility for unintended bias.
ARO 2018-9 is an investigator-initiated trial funded by Accuray. Dr. Bernhardt disclosed consulting actives, fees, travel expenses, and research funding from Accuray and others. Dr. Gondi disclosed honoraria from UpToDate.
A version of this article appeared on Medscape.com.
Short-course SBRT: Standard of care in prostate cancer?
SAN DIEGO – delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.
Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.
The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.
“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.
Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.
But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
An international trial
PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.
In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).
At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.
Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.
The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.
At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).
Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.
Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.
Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.
Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”
The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.
In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”
PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.
A version of this article first appeared on Medscape.com.
SAN DIEGO – delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.
Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.
The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.
“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.
Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.
But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
An international trial
PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.
In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).
At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.
Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.
The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.
At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).
Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.
Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.
Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.
Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”
The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.
In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”
PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.
A version of this article first appeared on Medscape.com.
SAN DIEGO – delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.
Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.
The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.
“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.
Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.
But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
An international trial
PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.
In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).
At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.
Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.
The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.
At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).
Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.
Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.
Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.
Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”
The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.
In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”
PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.
A version of this article first appeared on Medscape.com.
AT ASTRO 2023
Salvage option to replace transplant in r/r Hodgkin lymphoma?
SAN DIEGO –
Patients who received second-line chemoimmunotherapy with nivolumab-brentuximab vedotin, with or without bendamustine, and proceeded to involved-site radiation appeared to have similar survival outcomes to those who received the chemoimmunotherapy combination plus the current second-line standard of care, which includes high-dose therapy and autologous stem cell transplant.
Among 28 patients with low-risk relapsed or refractory Hodgkin lymphoma followed for a median of 32 months, 3-year event-free survival without autologous stem cell transplant was 86.9% and 3-year progression-free survival was 95%, reported Brad Hoppe, MD, MPH, from the Mayo Clinic in Jacksonville, Fla. In contrast, 1-year progression-free survival was 91% among the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant, according to results of a trial the investigators published online in Blood in late 2022.
The latest results from the phase 2 CheckMate 744 trial were reported at the annual meeting of the American Society of Radiation Oncology.
“The findings suggest that children, adolescents, and young adults with low-risk relapsed classic Hodgkin lymphoma can be salvaged with low-toxicity chemoimmunotherapy and may not require high-dose therapy and transplant for a cure,” Dr. Hoppe said in an oral abstract session.
Andrea Ng, MD, MPH, a radiation oncologist who specializes in treating patients with Hodgkin lymphoma and other hematologic malignancies, said that, while the number of patients in the study was small and the follow-up too short, this option is “certainly something that’s very promising for the future.”
“The use of transplant in relapsed patients, which we have been doing for decades, is based on two very old, small, randomized studies,” said Dr. Ng, from the Dana-Farber Cancer Institute in Boston, who moderated the session.
“So, do we really need to transplant everybody? In the back of our minds, we think that we may be overtreating some patients,” she said.
Several small, retrospective studies exploring treatment with conventional chemotherapy with or without radiation therapy and without transplant in patients with relapsed or refractory Hodgkin lymphoma have demonstrated only modest results.
The CheckMate 744 trial, however, was designed to examine a risk-adapted and response-adapted approach to treating children, adolescents, and young adults with relapsed or refractory classic Hodgkin lymphoma within the setting of modern immunotherapy and targeted therapy. This approach was developed jointly by investigators with the Children’s Oncology Group and Euronet.
In the nonrandomized trial, patients were stratified into low-risk or standard-risk disease categories based on an algorithm that included factors at the time of initial diagnosis and relapse.
Patients were considered low-risk for relapse in three scenarios: (1) if they had initial stage IA or IIA disease that relapsed at least 1 year after the end of therapy; (2) if they had initial stage IA or IIA disease that relapsed between 3 and 12 months from the end of therapy but had received no more than three cycles of chemotherapy and no radiation therapy; or (3) if they had initial stage IB, IIB, or IIIA disease that relapsed more than 12 months after the end of first-line therapy.
To be included in the low-risk category, patients also had to be free of B symptoms or extranodal disease, free of relapse in prior radiation therapy fields, and have no more than four sites of lymphoma.
Low-risk patients were treated with a combination of nivolumab and brentuximab vedotin, which could be followed by additional brentuximab vedotin and bendamustine for those with a suboptimal response. Patients who achieved complete molecular remission after induction went on to consolidation therapy with involved-site radiation at a total dose of 30 Gy.
Patients considered standard-risk for relapse received the same nivolumab-brentuximab vedotin combination, with or without bendamustine, and then went on to high-dose therapy and autologous stem cell transplant.
In other results for the previously mentioned study published in Blood, the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant had an objective response rate of 95% – 86% of patients achieved complete molecular remission, and 9% achieved partial molecular remission.
At ASTRO, Dr. Hoppe reported results for the 28 patients with low-risk disease. One patient discontinued nivolumab/brentuximab vedotin after two cycles because of skin toxicity and was lost to follow-up. Of the remaining 27 patients, 21 had complete molecular remission after four cycles of the combination, and these patients went on to an additional two cycles of the combination, with 19 of 21 receiving involved-site radiation consolidation.
Six patients who had either a partial molecular remission or no response were given two additional cycles of brentuximab vedotin plus bendamustine. Of this group, three went on to complete molecular remission and received involved-site radiation consolidation on protocol. The remaining three patients who did not experience complete molecular remission received involved-site radiation off protocol.
The rate of complete molecular remission after four cycles of induction was 82.1%, and the rate of partial molecular remission was 14.3%, for an objective response rate of 96.4%. The respective response rates with the addition of two cycles of brentuximab vedotin and bendamustine were 92.9% and 7.1%, for an objective response rate of 100%, Dr. Hoppe reported.
Overall, at a median follow-up of 32 months, the 3-year event-free survival rate without transplant was 86.9%, and the 3-year progression-free survival rate was 95%.
Treatment-related adverse events of any grade occurred in 22 patients (78.6%) after induction, with 7 of those events (25%) being grade 3 or 4 in severity. Grade 3 or 4 events consisted of skin and subcutaneous tissue disorders in 3 patients, elevated liver function tests in 3 patients, and blood and lymphatic system disorders in 1 patient.
There were no new toxicities detected within 100 days of treatment.
“The results that Dr. Hoppe showed us are really, really good,” Dr. Ng said. And “the volume of treatment is pretty tiny, so I think we can safely say that long-term toxicities are very, very minimal.”
The study was supported by Bristol-Myers Squibb in collaboration with Seagen, Euronet-Paediatric Hodgkin Lymphoma, and the Children’s Oncology Group. Dr. Hoppe reported serving on a scientific advisory committee for Merck. Dr. Ng reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
Patients who received second-line chemoimmunotherapy with nivolumab-brentuximab vedotin, with or without bendamustine, and proceeded to involved-site radiation appeared to have similar survival outcomes to those who received the chemoimmunotherapy combination plus the current second-line standard of care, which includes high-dose therapy and autologous stem cell transplant.
Among 28 patients with low-risk relapsed or refractory Hodgkin lymphoma followed for a median of 32 months, 3-year event-free survival without autologous stem cell transplant was 86.9% and 3-year progression-free survival was 95%, reported Brad Hoppe, MD, MPH, from the Mayo Clinic in Jacksonville, Fla. In contrast, 1-year progression-free survival was 91% among the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant, according to results of a trial the investigators published online in Blood in late 2022.
The latest results from the phase 2 CheckMate 744 trial were reported at the annual meeting of the American Society of Radiation Oncology.
“The findings suggest that children, adolescents, and young adults with low-risk relapsed classic Hodgkin lymphoma can be salvaged with low-toxicity chemoimmunotherapy and may not require high-dose therapy and transplant for a cure,” Dr. Hoppe said in an oral abstract session.
Andrea Ng, MD, MPH, a radiation oncologist who specializes in treating patients with Hodgkin lymphoma and other hematologic malignancies, said that, while the number of patients in the study was small and the follow-up too short, this option is “certainly something that’s very promising for the future.”
“The use of transplant in relapsed patients, which we have been doing for decades, is based on two very old, small, randomized studies,” said Dr. Ng, from the Dana-Farber Cancer Institute in Boston, who moderated the session.
“So, do we really need to transplant everybody? In the back of our minds, we think that we may be overtreating some patients,” she said.
Several small, retrospective studies exploring treatment with conventional chemotherapy with or without radiation therapy and without transplant in patients with relapsed or refractory Hodgkin lymphoma have demonstrated only modest results.
The CheckMate 744 trial, however, was designed to examine a risk-adapted and response-adapted approach to treating children, adolescents, and young adults with relapsed or refractory classic Hodgkin lymphoma within the setting of modern immunotherapy and targeted therapy. This approach was developed jointly by investigators with the Children’s Oncology Group and Euronet.
In the nonrandomized trial, patients were stratified into low-risk or standard-risk disease categories based on an algorithm that included factors at the time of initial diagnosis and relapse.
Patients were considered low-risk for relapse in three scenarios: (1) if they had initial stage IA or IIA disease that relapsed at least 1 year after the end of therapy; (2) if they had initial stage IA or IIA disease that relapsed between 3 and 12 months from the end of therapy but had received no more than three cycles of chemotherapy and no radiation therapy; or (3) if they had initial stage IB, IIB, or IIIA disease that relapsed more than 12 months after the end of first-line therapy.
To be included in the low-risk category, patients also had to be free of B symptoms or extranodal disease, free of relapse in prior radiation therapy fields, and have no more than four sites of lymphoma.
Low-risk patients were treated with a combination of nivolumab and brentuximab vedotin, which could be followed by additional brentuximab vedotin and bendamustine for those with a suboptimal response. Patients who achieved complete molecular remission after induction went on to consolidation therapy with involved-site radiation at a total dose of 30 Gy.
Patients considered standard-risk for relapse received the same nivolumab-brentuximab vedotin combination, with or without bendamustine, and then went on to high-dose therapy and autologous stem cell transplant.
In other results for the previously mentioned study published in Blood, the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant had an objective response rate of 95% – 86% of patients achieved complete molecular remission, and 9% achieved partial molecular remission.
At ASTRO, Dr. Hoppe reported results for the 28 patients with low-risk disease. One patient discontinued nivolumab/brentuximab vedotin after two cycles because of skin toxicity and was lost to follow-up. Of the remaining 27 patients, 21 had complete molecular remission after four cycles of the combination, and these patients went on to an additional two cycles of the combination, with 19 of 21 receiving involved-site radiation consolidation.
Six patients who had either a partial molecular remission or no response were given two additional cycles of brentuximab vedotin plus bendamustine. Of this group, three went on to complete molecular remission and received involved-site radiation consolidation on protocol. The remaining three patients who did not experience complete molecular remission received involved-site radiation off protocol.
The rate of complete molecular remission after four cycles of induction was 82.1%, and the rate of partial molecular remission was 14.3%, for an objective response rate of 96.4%. The respective response rates with the addition of two cycles of brentuximab vedotin and bendamustine were 92.9% and 7.1%, for an objective response rate of 100%, Dr. Hoppe reported.
Overall, at a median follow-up of 32 months, the 3-year event-free survival rate without transplant was 86.9%, and the 3-year progression-free survival rate was 95%.
Treatment-related adverse events of any grade occurred in 22 patients (78.6%) after induction, with 7 of those events (25%) being grade 3 or 4 in severity. Grade 3 or 4 events consisted of skin and subcutaneous tissue disorders in 3 patients, elevated liver function tests in 3 patients, and blood and lymphatic system disorders in 1 patient.
There were no new toxicities detected within 100 days of treatment.
“The results that Dr. Hoppe showed us are really, really good,” Dr. Ng said. And “the volume of treatment is pretty tiny, so I think we can safely say that long-term toxicities are very, very minimal.”
The study was supported by Bristol-Myers Squibb in collaboration with Seagen, Euronet-Paediatric Hodgkin Lymphoma, and the Children’s Oncology Group. Dr. Hoppe reported serving on a scientific advisory committee for Merck. Dr. Ng reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
Patients who received second-line chemoimmunotherapy with nivolumab-brentuximab vedotin, with or without bendamustine, and proceeded to involved-site radiation appeared to have similar survival outcomes to those who received the chemoimmunotherapy combination plus the current second-line standard of care, which includes high-dose therapy and autologous stem cell transplant.
Among 28 patients with low-risk relapsed or refractory Hodgkin lymphoma followed for a median of 32 months, 3-year event-free survival without autologous stem cell transplant was 86.9% and 3-year progression-free survival was 95%, reported Brad Hoppe, MD, MPH, from the Mayo Clinic in Jacksonville, Fla. In contrast, 1-year progression-free survival was 91% among the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant, according to results of a trial the investigators published online in Blood in late 2022.
The latest results from the phase 2 CheckMate 744 trial were reported at the annual meeting of the American Society of Radiation Oncology.
“The findings suggest that children, adolescents, and young adults with low-risk relapsed classic Hodgkin lymphoma can be salvaged with low-toxicity chemoimmunotherapy and may not require high-dose therapy and transplant for a cure,” Dr. Hoppe said in an oral abstract session.
Andrea Ng, MD, MPH, a radiation oncologist who specializes in treating patients with Hodgkin lymphoma and other hematologic malignancies, said that, while the number of patients in the study was small and the follow-up too short, this option is “certainly something that’s very promising for the future.”
“The use of transplant in relapsed patients, which we have been doing for decades, is based on two very old, small, randomized studies,” said Dr. Ng, from the Dana-Farber Cancer Institute in Boston, who moderated the session.
“So, do we really need to transplant everybody? In the back of our minds, we think that we may be overtreating some patients,” she said.
Several small, retrospective studies exploring treatment with conventional chemotherapy with or without radiation therapy and without transplant in patients with relapsed or refractory Hodgkin lymphoma have demonstrated only modest results.
The CheckMate 744 trial, however, was designed to examine a risk-adapted and response-adapted approach to treating children, adolescents, and young adults with relapsed or refractory classic Hodgkin lymphoma within the setting of modern immunotherapy and targeted therapy. This approach was developed jointly by investigators with the Children’s Oncology Group and Euronet.
In the nonrandomized trial, patients were stratified into low-risk or standard-risk disease categories based on an algorithm that included factors at the time of initial diagnosis and relapse.
Patients were considered low-risk for relapse in three scenarios: (1) if they had initial stage IA or IIA disease that relapsed at least 1 year after the end of therapy; (2) if they had initial stage IA or IIA disease that relapsed between 3 and 12 months from the end of therapy but had received no more than three cycles of chemotherapy and no radiation therapy; or (3) if they had initial stage IB, IIB, or IIIA disease that relapsed more than 12 months after the end of first-line therapy.
To be included in the low-risk category, patients also had to be free of B symptoms or extranodal disease, free of relapse in prior radiation therapy fields, and have no more than four sites of lymphoma.
Low-risk patients were treated with a combination of nivolumab and brentuximab vedotin, which could be followed by additional brentuximab vedotin and bendamustine for those with a suboptimal response. Patients who achieved complete molecular remission after induction went on to consolidation therapy with involved-site radiation at a total dose of 30 Gy.
Patients considered standard-risk for relapse received the same nivolumab-brentuximab vedotin combination, with or without bendamustine, and then went on to high-dose therapy and autologous stem cell transplant.
In other results for the previously mentioned study published in Blood, the 44 standard-risk patients who received high-dose therapy and autologous stem cell transplant had an objective response rate of 95% – 86% of patients achieved complete molecular remission, and 9% achieved partial molecular remission.
At ASTRO, Dr. Hoppe reported results for the 28 patients with low-risk disease. One patient discontinued nivolumab/brentuximab vedotin after two cycles because of skin toxicity and was lost to follow-up. Of the remaining 27 patients, 21 had complete molecular remission after four cycles of the combination, and these patients went on to an additional two cycles of the combination, with 19 of 21 receiving involved-site radiation consolidation.
Six patients who had either a partial molecular remission or no response were given two additional cycles of brentuximab vedotin plus bendamustine. Of this group, three went on to complete molecular remission and received involved-site radiation consolidation on protocol. The remaining three patients who did not experience complete molecular remission received involved-site radiation off protocol.
The rate of complete molecular remission after four cycles of induction was 82.1%, and the rate of partial molecular remission was 14.3%, for an objective response rate of 96.4%. The respective response rates with the addition of two cycles of brentuximab vedotin and bendamustine were 92.9% and 7.1%, for an objective response rate of 100%, Dr. Hoppe reported.
Overall, at a median follow-up of 32 months, the 3-year event-free survival rate without transplant was 86.9%, and the 3-year progression-free survival rate was 95%.
Treatment-related adverse events of any grade occurred in 22 patients (78.6%) after induction, with 7 of those events (25%) being grade 3 or 4 in severity. Grade 3 or 4 events consisted of skin and subcutaneous tissue disorders in 3 patients, elevated liver function tests in 3 patients, and blood and lymphatic system disorders in 1 patient.
There were no new toxicities detected within 100 days of treatment.
“The results that Dr. Hoppe showed us are really, really good,” Dr. Ng said. And “the volume of treatment is pretty tiny, so I think we can safely say that long-term toxicities are very, very minimal.”
The study was supported by Bristol-Myers Squibb in collaboration with Seagen, Euronet-Paediatric Hodgkin Lymphoma, and the Children’s Oncology Group. Dr. Hoppe reported serving on a scientific advisory committee for Merck. Dr. Ng reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
AT ASTRO 2023
Safely skip PET2 after brentuximab in Hodgkin lymphoma?
FROM SOHO 2023
Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.
These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.
Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.
However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.
Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.
Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.
In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.
In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.
Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.
Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.
During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.
Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”
In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.
The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SOHO 2023
Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.
These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.
Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.
However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.
Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.
Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.
In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.
In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.
Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.
Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.
During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.
Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”
In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.
The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SOHO 2023
Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.
These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.
Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.
However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.
Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.
Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.
In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.
In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.
Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.
Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.
During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.
Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”
In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.
The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Is additional treatment needed, pretransplant, for r/r AML?
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM SOHO 2023
Urine test shows promise for diagnosing urothelial carcinoma
, according to findings from a recent validation study.
The urinary comprehensive genomic profiling (uCGP) assay (UroAmp, Convergent Genomics) had a specificity of 95% and sensitivity of 90% for an initial diagnosis of urothelial carcinoma in patients with hematuria – identifying 95 of 100 people with urothelial carcinoma and 90 of 100 patients without the disease.
For patients under surveillance for urothelial cancer recurrence, the test was six times more accurate than traditional clinical risk factors for predicting recurrence.
“Considering its performance in multiple areas of urothelial carcinoma diagnosis and monitoring, uCGP shows great promise to enhance delivery of risk-stratified care,” Keyan Salari, MD, PhD, director of the prostate cancer genetics program at Massachusetts General Hospital in Boston, and colleagues wrote in a study published in Clinical Cancer Research.
“The idea is that this could be used as kind of a first-pass screening tool for patients with hematuria that could potentially obviate the need for undergoing imaging such as CT scans or cystoscopy,” Dr. Salari said in an interview.
The uCGP test is a next-generation sequencing assay that identifies mutations in 60 genes associated with bladder cancer. An earlier analysis evaluating the test as a potential screening tool focused on 10 key genes covered in the assay. The study found the test accurately predicted future bladder cancer in 66% of urine samples, including some that had been collected more than a decade prior to being tested.
In the current case-control study, Dr. Salari and colleagues used a total of 581 samples – 333 samples for classifying disease and developing algorithms for initial diagnosis, surveillance, and molecular-grade prediction, as well as 248 samples for blinded validation. The test’s performance was evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.
Overall, the test demonstrated a specificity of 95% and sensitivity of 90% for an initial urothelial carcinoma diagnosis, but performed even better for the most aggressive tumors, with 100% sensitivity for diagnosing high-grade urothelial carcinoma and muscle-invasive tumors.
On the diagnosis front, the test had a positive predictive value of 88% and a negative predictive value of 99%.
Among patients under surveillance, the test predicted the risk of recurrence significantly better than standard clinical risk factors (hazard ratio, 6.2). The test demonstrated a positive predictive value similar to that observed for cytology (45% vs. 42%) but a much higher sensitivity (79% vs. 25%). The test also demonstrated a negative predictive value of 91% for recurrence.
The molecular-grade algorithm performed well, with a positive predictive value for high-grade disease of 88% and a specificity of 95% in the validation cohort.
Overall, “uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients,” the authors concluded. The test is not currently reimbursed by Medicare, but negotiations with third-party payers are reportedly underway.
The study was supported by the National Cancer Institute. Dr. Salari reported grants from Convergent Genomics during the conduct of the study as well as grants from Urology Care Foundation and Prostate Cancer Foundation, and personal fees from OrigiMed outside the submitted work. Several coauthors are employees and stockholders of Convergent Genomics.
A version of this article first appeared on Medscape.com.
, according to findings from a recent validation study.
The urinary comprehensive genomic profiling (uCGP) assay (UroAmp, Convergent Genomics) had a specificity of 95% and sensitivity of 90% for an initial diagnosis of urothelial carcinoma in patients with hematuria – identifying 95 of 100 people with urothelial carcinoma and 90 of 100 patients without the disease.
For patients under surveillance for urothelial cancer recurrence, the test was six times more accurate than traditional clinical risk factors for predicting recurrence.
“Considering its performance in multiple areas of urothelial carcinoma diagnosis and monitoring, uCGP shows great promise to enhance delivery of risk-stratified care,” Keyan Salari, MD, PhD, director of the prostate cancer genetics program at Massachusetts General Hospital in Boston, and colleagues wrote in a study published in Clinical Cancer Research.
“The idea is that this could be used as kind of a first-pass screening tool for patients with hematuria that could potentially obviate the need for undergoing imaging such as CT scans or cystoscopy,” Dr. Salari said in an interview.
The uCGP test is a next-generation sequencing assay that identifies mutations in 60 genes associated with bladder cancer. An earlier analysis evaluating the test as a potential screening tool focused on 10 key genes covered in the assay. The study found the test accurately predicted future bladder cancer in 66% of urine samples, including some that had been collected more than a decade prior to being tested.
In the current case-control study, Dr. Salari and colleagues used a total of 581 samples – 333 samples for classifying disease and developing algorithms for initial diagnosis, surveillance, and molecular-grade prediction, as well as 248 samples for blinded validation. The test’s performance was evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.
Overall, the test demonstrated a specificity of 95% and sensitivity of 90% for an initial urothelial carcinoma diagnosis, but performed even better for the most aggressive tumors, with 100% sensitivity for diagnosing high-grade urothelial carcinoma and muscle-invasive tumors.
On the diagnosis front, the test had a positive predictive value of 88% and a negative predictive value of 99%.
Among patients under surveillance, the test predicted the risk of recurrence significantly better than standard clinical risk factors (hazard ratio, 6.2). The test demonstrated a positive predictive value similar to that observed for cytology (45% vs. 42%) but a much higher sensitivity (79% vs. 25%). The test also demonstrated a negative predictive value of 91% for recurrence.
The molecular-grade algorithm performed well, with a positive predictive value for high-grade disease of 88% and a specificity of 95% in the validation cohort.
Overall, “uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients,” the authors concluded. The test is not currently reimbursed by Medicare, but negotiations with third-party payers are reportedly underway.
The study was supported by the National Cancer Institute. Dr. Salari reported grants from Convergent Genomics during the conduct of the study as well as grants from Urology Care Foundation and Prostate Cancer Foundation, and personal fees from OrigiMed outside the submitted work. Several coauthors are employees and stockholders of Convergent Genomics.
A version of this article first appeared on Medscape.com.
, according to findings from a recent validation study.
The urinary comprehensive genomic profiling (uCGP) assay (UroAmp, Convergent Genomics) had a specificity of 95% and sensitivity of 90% for an initial diagnosis of urothelial carcinoma in patients with hematuria – identifying 95 of 100 people with urothelial carcinoma and 90 of 100 patients without the disease.
For patients under surveillance for urothelial cancer recurrence, the test was six times more accurate than traditional clinical risk factors for predicting recurrence.
“Considering its performance in multiple areas of urothelial carcinoma diagnosis and monitoring, uCGP shows great promise to enhance delivery of risk-stratified care,” Keyan Salari, MD, PhD, director of the prostate cancer genetics program at Massachusetts General Hospital in Boston, and colleagues wrote in a study published in Clinical Cancer Research.
“The idea is that this could be used as kind of a first-pass screening tool for patients with hematuria that could potentially obviate the need for undergoing imaging such as CT scans or cystoscopy,” Dr. Salari said in an interview.
The uCGP test is a next-generation sequencing assay that identifies mutations in 60 genes associated with bladder cancer. An earlier analysis evaluating the test as a potential screening tool focused on 10 key genes covered in the assay. The study found the test accurately predicted future bladder cancer in 66% of urine samples, including some that had been collected more than a decade prior to being tested.
In the current case-control study, Dr. Salari and colleagues used a total of 581 samples – 333 samples for classifying disease and developing algorithms for initial diagnosis, surveillance, and molecular-grade prediction, as well as 248 samples for blinded validation. The test’s performance was evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.
Overall, the test demonstrated a specificity of 95% and sensitivity of 90% for an initial urothelial carcinoma diagnosis, but performed even better for the most aggressive tumors, with 100% sensitivity for diagnosing high-grade urothelial carcinoma and muscle-invasive tumors.
On the diagnosis front, the test had a positive predictive value of 88% and a negative predictive value of 99%.
Among patients under surveillance, the test predicted the risk of recurrence significantly better than standard clinical risk factors (hazard ratio, 6.2). The test demonstrated a positive predictive value similar to that observed for cytology (45% vs. 42%) but a much higher sensitivity (79% vs. 25%). The test also demonstrated a negative predictive value of 91% for recurrence.
The molecular-grade algorithm performed well, with a positive predictive value for high-grade disease of 88% and a specificity of 95% in the validation cohort.
Overall, “uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients,” the authors concluded. The test is not currently reimbursed by Medicare, but negotiations with third-party payers are reportedly underway.
The study was supported by the National Cancer Institute. Dr. Salari reported grants from Convergent Genomics during the conduct of the study as well as grants from Urology Care Foundation and Prostate Cancer Foundation, and personal fees from OrigiMed outside the submitted work. Several coauthors are employees and stockholders of Convergent Genomics.
A version of this article first appeared on Medscape.com.
FROM CLINICAL CANCER RESEARCH
Do some randomized controlled trials stack the deck?
Randomized controlled trials in oncology can make or break an investigational drug, with both patient lives and pharmaceutical company profits at stake.
These trials typically pit two options against each other, an investigational therapy and a control therapy – often a standard of care – to see which has greater benefit.
But These biases may result in substandard care for trial participants, even harm, and can invalidate or dilute scientific findings.
One major issue is whether participants in the control arm of a trial receive the standard of care or active therapy after disease progression. In clinical trial parlance, this practice is called crossover.
Patients who do not receive standard-of-care therapy after disease progression may be “unfairly disadvantaged,” experts wrote in a commentary published in late June.What’s worse, optimal crossover does not always happen, commentary author Edward R. Scheffer Cliff, MBBS, MPH, from Brigham and Women’s Hospital in Boston said in an interview.
A recent example comes from the ADAURA trial comparing adjuvant therapy with osimertinib (Tagrisso) to placebo following complete resection of localized or locally advanced stage IB-IIIA non–small cell lung cancer (NSCLC) harboring EGFR mutations.
The trial, which began in November 2015, was unblinded early and halted on the recommendation of the independent data-monitoring committee because osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death. These data led to the Food and Drug Administration’s 2018 approval of osimertinib as first-line treatment in this setting.
The recent overall survival data from ADAURA, presented at the 2023 American Society of Clinical Oncology annual meeting, helped confirm the drug’s benefit: Osimertinib was associated with a 51% reduced risk for death, compared with placebo.
But critics of this report were troubled by the fact that, despite the reported benefits of osimertinib, only 79 of 205 patients (38.5%) in the control arm who relapsed received the drug – now considered standard of care in this setting.
The low rate of osimertinib crossover represents a serious flaw in the trial design and potentially an ethical problem.
In the commentary, Dr. Cliff, alongside colleagues Aaron S. Kesselheim, MD, JD, MPH, and William B. Feldman, MD, DPhil, MPH, detailed the ethical issues associated with substandard crossover in clinical trials.
“In the ethical design of clinical trials, patients make important sacrifices to participate, and in exchange, the academic and clinical communities owe them optimal treatment both during the intervention part of the trial and, if they progress, after progression, especially when it is directly in the control of the trial sponsor as to whether a drug that they produce is made available to a clinical trial participant,” Dr. Cliff and colleagues wrote.
The authors highlighted 10 clinical trials – including SHINE, ZUMA-7, CLL14, ALCYONE, and JAVELIN 100 – that had problematic crossover. In the SHINE trial, for instance, 39% of control arm patients with mantle cell lymphoma received BTKi therapy post progression, while in the ALCYONE trial of multiple myeloma, only 10% of control patients received daratumumab at first progression. The VISION trial had the lowest crossover rate, with only one control arm patient (0.5%) with metastatic castration-resistant prostate cancer receiving lutetium-PSMA-617 after progression.
“Depriving control arm patients access to standard-of-care post-RCT therapy also has important scientific implications,” Dr. Cliff and colleagues wrote. In oncology, “if patients in the control arm do not receive standard-of-care therapy after disease progression, then they are unfairly disadvantaged, and it becomes difficult to assess whether the intervention has indeed improved quality of life or survival.”
Clinical trials should be designed with both ethical behavior and scientific integrity in mind, Dr. Cliff told this news organization. It’s incumbent on everyone directly or peripherally involved in randomized trials to ensure that they are designed with mandatory unblinding at the time of disease progression, and that crossover is both allowed and funded by the trial sponsor and mandated by the trial investigators and FDA.
When it comes to clinical trials and the sacrifices patients make to participate, “I think everyone needs to lift their game,” Dr. Cliff said.
The commentary by Dr. Cliff and colleagues was supported by Arnold Ventures. Dr. Cliff disclosed institutional funding from the firm. Dr. Kesselheim reported reimbursement for expert testimony. Dr. Feldman reported consulting for Alosa Health and Aetion, and expert testimony on litigation.
A version of this article appeared on Medscape.com.
Randomized controlled trials in oncology can make or break an investigational drug, with both patient lives and pharmaceutical company profits at stake.
These trials typically pit two options against each other, an investigational therapy and a control therapy – often a standard of care – to see which has greater benefit.
But These biases may result in substandard care for trial participants, even harm, and can invalidate or dilute scientific findings.
One major issue is whether participants in the control arm of a trial receive the standard of care or active therapy after disease progression. In clinical trial parlance, this practice is called crossover.
Patients who do not receive standard-of-care therapy after disease progression may be “unfairly disadvantaged,” experts wrote in a commentary published in late June.What’s worse, optimal crossover does not always happen, commentary author Edward R. Scheffer Cliff, MBBS, MPH, from Brigham and Women’s Hospital in Boston said in an interview.
A recent example comes from the ADAURA trial comparing adjuvant therapy with osimertinib (Tagrisso) to placebo following complete resection of localized or locally advanced stage IB-IIIA non–small cell lung cancer (NSCLC) harboring EGFR mutations.
The trial, which began in November 2015, was unblinded early and halted on the recommendation of the independent data-monitoring committee because osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death. These data led to the Food and Drug Administration’s 2018 approval of osimertinib as first-line treatment in this setting.
The recent overall survival data from ADAURA, presented at the 2023 American Society of Clinical Oncology annual meeting, helped confirm the drug’s benefit: Osimertinib was associated with a 51% reduced risk for death, compared with placebo.
But critics of this report were troubled by the fact that, despite the reported benefits of osimertinib, only 79 of 205 patients (38.5%) in the control arm who relapsed received the drug – now considered standard of care in this setting.
The low rate of osimertinib crossover represents a serious flaw in the trial design and potentially an ethical problem.
In the commentary, Dr. Cliff, alongside colleagues Aaron S. Kesselheim, MD, JD, MPH, and William B. Feldman, MD, DPhil, MPH, detailed the ethical issues associated with substandard crossover in clinical trials.
“In the ethical design of clinical trials, patients make important sacrifices to participate, and in exchange, the academic and clinical communities owe them optimal treatment both during the intervention part of the trial and, if they progress, after progression, especially when it is directly in the control of the trial sponsor as to whether a drug that they produce is made available to a clinical trial participant,” Dr. Cliff and colleagues wrote.
The authors highlighted 10 clinical trials – including SHINE, ZUMA-7, CLL14, ALCYONE, and JAVELIN 100 – that had problematic crossover. In the SHINE trial, for instance, 39% of control arm patients with mantle cell lymphoma received BTKi therapy post progression, while in the ALCYONE trial of multiple myeloma, only 10% of control patients received daratumumab at first progression. The VISION trial had the lowest crossover rate, with only one control arm patient (0.5%) with metastatic castration-resistant prostate cancer receiving lutetium-PSMA-617 after progression.
“Depriving control arm patients access to standard-of-care post-RCT therapy also has important scientific implications,” Dr. Cliff and colleagues wrote. In oncology, “if patients in the control arm do not receive standard-of-care therapy after disease progression, then they are unfairly disadvantaged, and it becomes difficult to assess whether the intervention has indeed improved quality of life or survival.”
Clinical trials should be designed with both ethical behavior and scientific integrity in mind, Dr. Cliff told this news organization. It’s incumbent on everyone directly or peripherally involved in randomized trials to ensure that they are designed with mandatory unblinding at the time of disease progression, and that crossover is both allowed and funded by the trial sponsor and mandated by the trial investigators and FDA.
When it comes to clinical trials and the sacrifices patients make to participate, “I think everyone needs to lift their game,” Dr. Cliff said.
The commentary by Dr. Cliff and colleagues was supported by Arnold Ventures. Dr. Cliff disclosed institutional funding from the firm. Dr. Kesselheim reported reimbursement for expert testimony. Dr. Feldman reported consulting for Alosa Health and Aetion, and expert testimony on litigation.
A version of this article appeared on Medscape.com.
Randomized controlled trials in oncology can make or break an investigational drug, with both patient lives and pharmaceutical company profits at stake.
These trials typically pit two options against each other, an investigational therapy and a control therapy – often a standard of care – to see which has greater benefit.
But These biases may result in substandard care for trial participants, even harm, and can invalidate or dilute scientific findings.
One major issue is whether participants in the control arm of a trial receive the standard of care or active therapy after disease progression. In clinical trial parlance, this practice is called crossover.
Patients who do not receive standard-of-care therapy after disease progression may be “unfairly disadvantaged,” experts wrote in a commentary published in late June.What’s worse, optimal crossover does not always happen, commentary author Edward R. Scheffer Cliff, MBBS, MPH, from Brigham and Women’s Hospital in Boston said in an interview.
A recent example comes from the ADAURA trial comparing adjuvant therapy with osimertinib (Tagrisso) to placebo following complete resection of localized or locally advanced stage IB-IIIA non–small cell lung cancer (NSCLC) harboring EGFR mutations.
The trial, which began in November 2015, was unblinded early and halted on the recommendation of the independent data-monitoring committee because osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death. These data led to the Food and Drug Administration’s 2018 approval of osimertinib as first-line treatment in this setting.
The recent overall survival data from ADAURA, presented at the 2023 American Society of Clinical Oncology annual meeting, helped confirm the drug’s benefit: Osimertinib was associated with a 51% reduced risk for death, compared with placebo.
But critics of this report were troubled by the fact that, despite the reported benefits of osimertinib, only 79 of 205 patients (38.5%) in the control arm who relapsed received the drug – now considered standard of care in this setting.
The low rate of osimertinib crossover represents a serious flaw in the trial design and potentially an ethical problem.
In the commentary, Dr. Cliff, alongside colleagues Aaron S. Kesselheim, MD, JD, MPH, and William B. Feldman, MD, DPhil, MPH, detailed the ethical issues associated with substandard crossover in clinical trials.
“In the ethical design of clinical trials, patients make important sacrifices to participate, and in exchange, the academic and clinical communities owe them optimal treatment both during the intervention part of the trial and, if they progress, after progression, especially when it is directly in the control of the trial sponsor as to whether a drug that they produce is made available to a clinical trial participant,” Dr. Cliff and colleagues wrote.
The authors highlighted 10 clinical trials – including SHINE, ZUMA-7, CLL14, ALCYONE, and JAVELIN 100 – that had problematic crossover. In the SHINE trial, for instance, 39% of control arm patients with mantle cell lymphoma received BTKi therapy post progression, while in the ALCYONE trial of multiple myeloma, only 10% of control patients received daratumumab at first progression. The VISION trial had the lowest crossover rate, with only one control arm patient (0.5%) with metastatic castration-resistant prostate cancer receiving lutetium-PSMA-617 after progression.
“Depriving control arm patients access to standard-of-care post-RCT therapy also has important scientific implications,” Dr. Cliff and colleagues wrote. In oncology, “if patients in the control arm do not receive standard-of-care therapy after disease progression, then they are unfairly disadvantaged, and it becomes difficult to assess whether the intervention has indeed improved quality of life or survival.”
Clinical trials should be designed with both ethical behavior and scientific integrity in mind, Dr. Cliff told this news organization. It’s incumbent on everyone directly or peripherally involved in randomized trials to ensure that they are designed with mandatory unblinding at the time of disease progression, and that crossover is both allowed and funded by the trial sponsor and mandated by the trial investigators and FDA.
When it comes to clinical trials and the sacrifices patients make to participate, “I think everyone needs to lift their game,” Dr. Cliff said.
The commentary by Dr. Cliff and colleagues was supported by Arnold Ventures. Dr. Cliff disclosed institutional funding from the firm. Dr. Kesselheim reported reimbursement for expert testimony. Dr. Feldman reported consulting for Alosa Health and Aetion, and expert testimony on litigation.
A version of this article appeared on Medscape.com.
FROM ASCO 2023
Does private equity ensure survival of GI practices?
CHICAGO – In this age of corporate megamergers, private practice gastroenterologists are increasingly weighing the pros and cons of selling their practices to private equity firms.
It’s becoming more difficult for solo or small group practices to go it alone. While there may be advantages in selling a medical practice to a private equity firm, physicians could be trading a degree of freedom for financial certainty and relief from administrative burdens, according to Klaus Mergener, MD, PhD, MBA, AGAF, a clinical gastroenterologist, affiliate professor of medicine at the University of Washington, Seattle, and chief medical officer of Pentax Medical’s Lifecare Division.
“Over the last decades, and ongoing, there have been massive downward pressures on reimbursements and costs are rising. Practices have tried to compensate, and they’ve added ancillary revenue streams, and they’ve tried to cut costs internally. It’s fair to say that depending on the local market, many practices find that one of the last viable options is essentially to spread overhead costs – meaning you have to get larger and you have to merge into larger entities,” he said on May 6 during a presentation at the annual Digestive Diseases Week® meeting.
The first independent gastroenterology practice was purchased by a private equity firm in 2016. Today, more than 1,000 gastroenterologists have been acquired by private equity firms, which amounts to a total value in excess of $1 billion.
The pace at which private equity firms are buying private medical practices is accelerating. On April 26, Kaiser Permanente – with 39 hospitals and 24,000 physicians – announced that it had acquired Geisinger Health System, a regional health care provider in Pennsylvania with 10 hospitals, forming a new entity called Risant Health.
Dr. Mergener likened the situation to the story of David and Goliath. David famously defeated the much larger and more powerful Goliath, but the metaphor is imperfect, because small private practices are running out of rocks to sling at the big guys.
In some small, rural markets with no significant competition, it may be possible for small practices to survive through mergers, “but in most U.S. markets, it’s fair to say that ... practices have found it hard to merge without external help. There are egos involved, there are many hurdles, and this is where private equity has essentially moved in as catalyst,” Dr. Mergener said.
Employees of large entities
Other physicians, however, say that while acquisition may seem inevitable, private equity is an option for survival.
“I don’t think this means the demise of private practice,“ said Lawrence R. Kosinski, MD, MBA, AGAF , chief medical officer at SonarMD, a Chicago-based company that specializes in facilitating managing the care of patients with chronic conditions.
“I think that private equity is just another way of aggregating GI doctors into an employment situation,” he said. “It’s just a different tool, and we can argue all day as to whether it’s the right tool, but it’s a tool no different than employment by a hospital. You can work for a hospital or you can work for a private equity funded group, but in the end, you’re an employee of a large entity.”
Michael Weinstein, MD, AGAF, president and CEO of Capital Digestive Care, a practice in Washington, and managing partner of the Metropolitan Gastroenterology Group Division, a medical group practice in Silver Spring, Md., advised taking a long and hard look before taking the leap into the hands of private equity.
“You have to have a strategy, but you have to know what you have and what you need. Ask yourself whether private equity is what you really need. They’re not in the business of making you a better practice,” he said. “Once you do it, you’re no longer in control of your future. Somebody else is in control of your future.”
Private equity firms sell a bill of goods
“They say, ‘We’re going to improve your services, we’re going to bring you tech, we’re going to negotiate better contracts and do all these things for you.’ Ninety percent of it is a lie, because that’s not what they’re going to do. They’re just going to try to increase the bottom line, bolt down a few more practices, increase the gross revenue, and thereby increase the net profit from where it was before, not necessarily because they’re making better lives for the individual providers. They’re just adding more cows to the field, but every cow is the same as far as they’re concerned. They really don’t care about the production of milk,” Dr. Weinstein said.
A few years ago, his practice considered whether private equity would be a good option. His practice, he said, needed to be bigger and more effective and efficient. Instead, his practice formed a partnership with PE GI Solutions (formerly Physicians Endoscopy), a developer and manager of endoscopic ambulatory surgery centers.
In Dallas, private equity firms have increased reimbursements for Texas Digestive Disease Consultants.
“Our practice went through mergers, acquisitions, and now, with private equity coming onto the scene, it’s completely different,” said Kimberly M. Persley, MD, AGAF, a partner with Texas Digestive Disease Consultants and a member of the GI & Hepatology News board of editors.
“We were a five-person independent group negotiating contracts, getting cut every other year by some payer because they negotiated a better price with someone else. And having to go through that process every year when all we really want to do is take care of patients. Private equity adds to our group practice by having someone dedicated to negotiating these contracts, and getting reimbursed far more than we ever did prior to our involvement with private equity,” she said.
How it works
In the typical model, a private equity partner purchases the practice and creates a management services organization (MSO), which provides nonclinical services to the practice, theoretically freeing the physicians from the administrative burdens of day-to-day practice.
The practice then becomes the care center managed by the MSO, and the physicians in the practice at the time of the acquisition get stock in the MSO. “They sell a portion of their annual income, so going forward they’re making less money initially, until some of that is being recovered by higher efficiencies. They get an upfront check at a multiple of the income they just sold, and that provides the initial incentive. Then the entity is grown by adding other practices through the same mechanism,” Dr. Mergener said.
After about 5 years, the private equity partner typically sells the MSO to another, probably even larger buyer, and the cycle starts again.
In addition to the upfront incentive that makes practice mergers and consolidation work, the arrangement gives the GI practice access to top-notch administrators, as well as access to capital for investments such as information technology infrastructure, digital health, and data analytics.
He cautioned that it’s crucial for practices to enter the marriage with eyes wide open and be very careful in choosing the private equity partner.
“The goal is to find a partner that has values and a vision that matches the practice’s. In theory, they should be pulling on the same side of the rope, because if it’s a high-quality practice and efficiencies are being improved, more practices should be more likely to join,” which will benefit physicians, patients, and the private equity partner alike, Dr. Mergener said.
Although the private equity construct has been successful in the short term for many practices, it’s less clear what will happen long-term. There is a risk that after 5 years there won’t be a buyer for the MSO at the expected price, which may result in complex financial transactions that could leave the MSO in debt. In such a scenario, physician employees would not be personally liable, but might suffer the consequences of a failing or unsuccessful operation, Dr. Mergener said.
Dr. Mergener’s talk was presented as part of a an ASGE Presidential Plenary held during DDW 2023. He disclosed consulting, honoraria, advisory board activity or stock options from various corporations, but reported having no relationships with private equity.
DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – In this age of corporate megamergers, private practice gastroenterologists are increasingly weighing the pros and cons of selling their practices to private equity firms.
It’s becoming more difficult for solo or small group practices to go it alone. While there may be advantages in selling a medical practice to a private equity firm, physicians could be trading a degree of freedom for financial certainty and relief from administrative burdens, according to Klaus Mergener, MD, PhD, MBA, AGAF, a clinical gastroenterologist, affiliate professor of medicine at the University of Washington, Seattle, and chief medical officer of Pentax Medical’s Lifecare Division.
“Over the last decades, and ongoing, there have been massive downward pressures on reimbursements and costs are rising. Practices have tried to compensate, and they’ve added ancillary revenue streams, and they’ve tried to cut costs internally. It’s fair to say that depending on the local market, many practices find that one of the last viable options is essentially to spread overhead costs – meaning you have to get larger and you have to merge into larger entities,” he said on May 6 during a presentation at the annual Digestive Diseases Week® meeting.
The first independent gastroenterology practice was purchased by a private equity firm in 2016. Today, more than 1,000 gastroenterologists have been acquired by private equity firms, which amounts to a total value in excess of $1 billion.
The pace at which private equity firms are buying private medical practices is accelerating. On April 26, Kaiser Permanente – with 39 hospitals and 24,000 physicians – announced that it had acquired Geisinger Health System, a regional health care provider in Pennsylvania with 10 hospitals, forming a new entity called Risant Health.
Dr. Mergener likened the situation to the story of David and Goliath. David famously defeated the much larger and more powerful Goliath, but the metaphor is imperfect, because small private practices are running out of rocks to sling at the big guys.
In some small, rural markets with no significant competition, it may be possible for small practices to survive through mergers, “but in most U.S. markets, it’s fair to say that ... practices have found it hard to merge without external help. There are egos involved, there are many hurdles, and this is where private equity has essentially moved in as catalyst,” Dr. Mergener said.
Employees of large entities
Other physicians, however, say that while acquisition may seem inevitable, private equity is an option for survival.
“I don’t think this means the demise of private practice,“ said Lawrence R. Kosinski, MD, MBA, AGAF , chief medical officer at SonarMD, a Chicago-based company that specializes in facilitating managing the care of patients with chronic conditions.
“I think that private equity is just another way of aggregating GI doctors into an employment situation,” he said. “It’s just a different tool, and we can argue all day as to whether it’s the right tool, but it’s a tool no different than employment by a hospital. You can work for a hospital or you can work for a private equity funded group, but in the end, you’re an employee of a large entity.”
Michael Weinstein, MD, AGAF, president and CEO of Capital Digestive Care, a practice in Washington, and managing partner of the Metropolitan Gastroenterology Group Division, a medical group practice in Silver Spring, Md., advised taking a long and hard look before taking the leap into the hands of private equity.
“You have to have a strategy, but you have to know what you have and what you need. Ask yourself whether private equity is what you really need. They’re not in the business of making you a better practice,” he said. “Once you do it, you’re no longer in control of your future. Somebody else is in control of your future.”
Private equity firms sell a bill of goods
“They say, ‘We’re going to improve your services, we’re going to bring you tech, we’re going to negotiate better contracts and do all these things for you.’ Ninety percent of it is a lie, because that’s not what they’re going to do. They’re just going to try to increase the bottom line, bolt down a few more practices, increase the gross revenue, and thereby increase the net profit from where it was before, not necessarily because they’re making better lives for the individual providers. They’re just adding more cows to the field, but every cow is the same as far as they’re concerned. They really don’t care about the production of milk,” Dr. Weinstein said.
A few years ago, his practice considered whether private equity would be a good option. His practice, he said, needed to be bigger and more effective and efficient. Instead, his practice formed a partnership with PE GI Solutions (formerly Physicians Endoscopy), a developer and manager of endoscopic ambulatory surgery centers.
In Dallas, private equity firms have increased reimbursements for Texas Digestive Disease Consultants.
“Our practice went through mergers, acquisitions, and now, with private equity coming onto the scene, it’s completely different,” said Kimberly M. Persley, MD, AGAF, a partner with Texas Digestive Disease Consultants and a member of the GI & Hepatology News board of editors.
“We were a five-person independent group negotiating contracts, getting cut every other year by some payer because they negotiated a better price with someone else. And having to go through that process every year when all we really want to do is take care of patients. Private equity adds to our group practice by having someone dedicated to negotiating these contracts, and getting reimbursed far more than we ever did prior to our involvement with private equity,” she said.
How it works
In the typical model, a private equity partner purchases the practice and creates a management services organization (MSO), which provides nonclinical services to the practice, theoretically freeing the physicians from the administrative burdens of day-to-day practice.
The practice then becomes the care center managed by the MSO, and the physicians in the practice at the time of the acquisition get stock in the MSO. “They sell a portion of their annual income, so going forward they’re making less money initially, until some of that is being recovered by higher efficiencies. They get an upfront check at a multiple of the income they just sold, and that provides the initial incentive. Then the entity is grown by adding other practices through the same mechanism,” Dr. Mergener said.
After about 5 years, the private equity partner typically sells the MSO to another, probably even larger buyer, and the cycle starts again.
In addition to the upfront incentive that makes practice mergers and consolidation work, the arrangement gives the GI practice access to top-notch administrators, as well as access to capital for investments such as information technology infrastructure, digital health, and data analytics.
He cautioned that it’s crucial for practices to enter the marriage with eyes wide open and be very careful in choosing the private equity partner.
“The goal is to find a partner that has values and a vision that matches the practice’s. In theory, they should be pulling on the same side of the rope, because if it’s a high-quality practice and efficiencies are being improved, more practices should be more likely to join,” which will benefit physicians, patients, and the private equity partner alike, Dr. Mergener said.
Although the private equity construct has been successful in the short term for many practices, it’s less clear what will happen long-term. There is a risk that after 5 years there won’t be a buyer for the MSO at the expected price, which may result in complex financial transactions that could leave the MSO in debt. In such a scenario, physician employees would not be personally liable, but might suffer the consequences of a failing or unsuccessful operation, Dr. Mergener said.
Dr. Mergener’s talk was presented as part of a an ASGE Presidential Plenary held during DDW 2023. He disclosed consulting, honoraria, advisory board activity or stock options from various corporations, but reported having no relationships with private equity.
DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – In this age of corporate megamergers, private practice gastroenterologists are increasingly weighing the pros and cons of selling their practices to private equity firms.
It’s becoming more difficult for solo or small group practices to go it alone. While there may be advantages in selling a medical practice to a private equity firm, physicians could be trading a degree of freedom for financial certainty and relief from administrative burdens, according to Klaus Mergener, MD, PhD, MBA, AGAF, a clinical gastroenterologist, affiliate professor of medicine at the University of Washington, Seattle, and chief medical officer of Pentax Medical’s Lifecare Division.
“Over the last decades, and ongoing, there have been massive downward pressures on reimbursements and costs are rising. Practices have tried to compensate, and they’ve added ancillary revenue streams, and they’ve tried to cut costs internally. It’s fair to say that depending on the local market, many practices find that one of the last viable options is essentially to spread overhead costs – meaning you have to get larger and you have to merge into larger entities,” he said on May 6 during a presentation at the annual Digestive Diseases Week® meeting.
The first independent gastroenterology practice was purchased by a private equity firm in 2016. Today, more than 1,000 gastroenterologists have been acquired by private equity firms, which amounts to a total value in excess of $1 billion.
The pace at which private equity firms are buying private medical practices is accelerating. On April 26, Kaiser Permanente – with 39 hospitals and 24,000 physicians – announced that it had acquired Geisinger Health System, a regional health care provider in Pennsylvania with 10 hospitals, forming a new entity called Risant Health.
Dr. Mergener likened the situation to the story of David and Goliath. David famously defeated the much larger and more powerful Goliath, but the metaphor is imperfect, because small private practices are running out of rocks to sling at the big guys.
In some small, rural markets with no significant competition, it may be possible for small practices to survive through mergers, “but in most U.S. markets, it’s fair to say that ... practices have found it hard to merge without external help. There are egos involved, there are many hurdles, and this is where private equity has essentially moved in as catalyst,” Dr. Mergener said.
Employees of large entities
Other physicians, however, say that while acquisition may seem inevitable, private equity is an option for survival.
“I don’t think this means the demise of private practice,“ said Lawrence R. Kosinski, MD, MBA, AGAF , chief medical officer at SonarMD, a Chicago-based company that specializes in facilitating managing the care of patients with chronic conditions.
“I think that private equity is just another way of aggregating GI doctors into an employment situation,” he said. “It’s just a different tool, and we can argue all day as to whether it’s the right tool, but it’s a tool no different than employment by a hospital. You can work for a hospital or you can work for a private equity funded group, but in the end, you’re an employee of a large entity.”
Michael Weinstein, MD, AGAF, president and CEO of Capital Digestive Care, a practice in Washington, and managing partner of the Metropolitan Gastroenterology Group Division, a medical group practice in Silver Spring, Md., advised taking a long and hard look before taking the leap into the hands of private equity.
“You have to have a strategy, but you have to know what you have and what you need. Ask yourself whether private equity is what you really need. They’re not in the business of making you a better practice,” he said. “Once you do it, you’re no longer in control of your future. Somebody else is in control of your future.”
Private equity firms sell a bill of goods
“They say, ‘We’re going to improve your services, we’re going to bring you tech, we’re going to negotiate better contracts and do all these things for you.’ Ninety percent of it is a lie, because that’s not what they’re going to do. They’re just going to try to increase the bottom line, bolt down a few more practices, increase the gross revenue, and thereby increase the net profit from where it was before, not necessarily because they’re making better lives for the individual providers. They’re just adding more cows to the field, but every cow is the same as far as they’re concerned. They really don’t care about the production of milk,” Dr. Weinstein said.
A few years ago, his practice considered whether private equity would be a good option. His practice, he said, needed to be bigger and more effective and efficient. Instead, his practice formed a partnership with PE GI Solutions (formerly Physicians Endoscopy), a developer and manager of endoscopic ambulatory surgery centers.
In Dallas, private equity firms have increased reimbursements for Texas Digestive Disease Consultants.
“Our practice went through mergers, acquisitions, and now, with private equity coming onto the scene, it’s completely different,” said Kimberly M. Persley, MD, AGAF, a partner with Texas Digestive Disease Consultants and a member of the GI & Hepatology News board of editors.
“We were a five-person independent group negotiating contracts, getting cut every other year by some payer because they negotiated a better price with someone else. And having to go through that process every year when all we really want to do is take care of patients. Private equity adds to our group practice by having someone dedicated to negotiating these contracts, and getting reimbursed far more than we ever did prior to our involvement with private equity,” she said.
How it works
In the typical model, a private equity partner purchases the practice and creates a management services organization (MSO), which provides nonclinical services to the practice, theoretically freeing the physicians from the administrative burdens of day-to-day practice.
The practice then becomes the care center managed by the MSO, and the physicians in the practice at the time of the acquisition get stock in the MSO. “They sell a portion of their annual income, so going forward they’re making less money initially, until some of that is being recovered by higher efficiencies. They get an upfront check at a multiple of the income they just sold, and that provides the initial incentive. Then the entity is grown by adding other practices through the same mechanism,” Dr. Mergener said.
After about 5 years, the private equity partner typically sells the MSO to another, probably even larger buyer, and the cycle starts again.
In addition to the upfront incentive that makes practice mergers and consolidation work, the arrangement gives the GI practice access to top-notch administrators, as well as access to capital for investments such as information technology infrastructure, digital health, and data analytics.
He cautioned that it’s crucial for practices to enter the marriage with eyes wide open and be very careful in choosing the private equity partner.
“The goal is to find a partner that has values and a vision that matches the practice’s. In theory, they should be pulling on the same side of the rope, because if it’s a high-quality practice and efficiencies are being improved, more practices should be more likely to join,” which will benefit physicians, patients, and the private equity partner alike, Dr. Mergener said.
Although the private equity construct has been successful in the short term for many practices, it’s less clear what will happen long-term. There is a risk that after 5 years there won’t be a buyer for the MSO at the expected price, which may result in complex financial transactions that could leave the MSO in debt. In such a scenario, physician employees would not be personally liable, but might suffer the consequences of a failing or unsuccessful operation, Dr. Mergener said.
Dr. Mergener’s talk was presented as part of a an ASGE Presidential Plenary held during DDW 2023. He disclosed consulting, honoraria, advisory board activity or stock options from various corporations, but reported having no relationships with private equity.
DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
AT DDW 2023
Geriatric care principles should apply to ICUs as well
Baseball legend Leroy “Satchel” Paige famously said that “age is a question of mind over matter: If you don’t mind, it doesn’t matter.”
But even the strongest and most supple minds can’t avoid the effects of advanced age and accompanying physical frailty, and for community-dwelling elderly with pulmonary diseases frailty is a predictor of both hospitalization and death, investigators have found.
For example, among 1,188 community-dwelling older adults enrolled in the Toledo (Spain) Study for Healthy Aging, declining pulmonary function measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was associated with increased risk for frailty and hospitalization, and a more than twofold greater risk for death in participants both with and without respiratory diseases. These findings were reported by Walter Sepulveda-Loyola, PT, MSC, PhD, from the Faculty of Health and Social Sciences at Universidad de Las Americas in Santiago, Chile, and colleagues in the journal Heart & Lung.
Similarly, results of a meta-analysis performed by investigators at Jiangsu (China) University showed that among 13,203 patients with chronic obstructive pulmonary disease (COPD), frailty was associated with a more than 2.6-fold relative increase in risk for death from any cause, and “prefrailty,” an intermediate state between frailty and “robustness,” was associated with a 48% relative increase in all-cause mortality. Frailty was also associated with a 2.2-fold risk for COPD exacerbations of any severity, the authors reported in JAMDA: The Journal of Post-Acute and Long-Term Care Medicine.
The good (old) USA
In June 2023 the U.S. Census Bureau announced that the median age of the U.S. population is now 38.9 years, and according to a 2016 Census Bureau report funded by the National Institutes of Health, “America’s 65-and-over population is projected to nearly double over the next three decades, from 48 million to 88 million by 2050.”
With the graying of the U.S. population the burden on pulmonary and critical care experts will almost inevitably increase, as evidenced by research from Julien Cobert, MD, from the University of California, San Francisco, and colleagues.
The investigators looked at trends over time in older adults admitted to ICUs from 1988 through 2015 using data from the Health and Retirement Study (HRS), a nationally representative, longitudinal study of older adults. They found that rates of preexisting frailty, disability, and multimorbidity increased over the study period.
“Our findings suggest a growing prevalence of geriatric conditions among older adults admitted to the ICU, suggesting a pressing need to integrate geriatric principles into critical care medicine. Further research could examine if early interventions emphasizing physical, cognitive, mental health, delirium prevention, advance care planning, and rehabilitation individualized to critically ill elderly patients with preexisting geriatric conditions could improve ICU outcomes and post-ICU recovery,” they wrote in a study published in the journal CHEST.
In an editorial accompanying the study by Dr. Cobert and colleagues, Nathan E. Brummel, MD, from The Ohio State University College of Medicine and Davis Heart and Lung Research Institute in Columbus, said “the finding that nearly 30% of overall HRS participants were admitted to the ICU provides novel data about the extent to which older Americans are affected by critical illness. Because the number of older Americans is projected to continue to increase for the next 30 years or more, these data make clear the ongoing importance of aging-focused research and clinical care.”
Dr. Brummel also noted that older adults who are admitted to the ICU today are at greater risk for poor outcomes than those admitted in prior years, as evidenced by the increased prevalence of disability, frailty, and multimorbidity.
“Moreover, because the average age of those admitted to the ICU only changed by 1 year during the study, these data show that increases in vulnerability are not simply due to chronological age, and they suggest that to identify those with greater baseline vulnerability, screening for geriatric syndromes at ICU admission may be warranted,” he wrote.
Geriatric principles in the ICU
“I think what’s most important is that we think about patients from a geriatric principles standpoint, not just when they’re admitted to the hospital but especially when they’re admitted to the ICU,” Dr. Cobert said in an interview.
“The first step is ensuring that we’re asking questions about their underlying comorbidities, especially around frailty, hearing, vision loss, falls, multimorbidities, polypharmacy – things that are primarily done on the outpatient side in geriatric clinics, but things that we should probably be a little bit more cognizant of, given that we’re starting to see higher rates of patients coming in with these issues,” he said.
Critical care specialists need to take a more holistic approach and try to understand as best they can each patients’ goals and then determine whether the ICU staff are acting in concordance with those goals, he emphasized.
For example, ICU clinicians should try to understand whether patients were losing function or having mobility difficulties before hospital and ICU admission, and what they hope to retain when or if they are discharged. ICU staff can then try as much as reasonably possible to minimize interventions that could contribute to impairment after discharge.
Frailty and COPD in the ICU
There are special considerations for frail elderly with obstructive airway disease, Dr. Cobert noted.
Patients with advanced COPD, for example, are likely to be on home oxygen.
“Home oxygen is a big deal,” he said. “It can definitely help with functioning and there’s potentially a mortality benefit in certain populations. But that said, it’s a flammable object that they have to carry around and lug with them all the time. It contributes to falls, it’s tethering, it’s life-limiting in many ways.”
In addition, many patients with COPD have multiple re-hospitalizations, and for clinicians the challenge is “understanding what their goals are, what their motivations are, especially when they live with dyspnea, with advanced lung disease. Is intubation within their goals of care? Has their functional status been declining over time? Are there things that we can optimize holistically and globally as their COPD advances over time?”
Another important component of critical care for the frail elderly is consideration of patients’ palliative care needs and what their symptoms and symptom burdens were like prior to hospitalizations.
“The ICU experience and the critical illness experience may serve as an inflexion point – more likely a downward inflection point – whereby their needs increase, their symptoms can worsen, and their health, especially their global health, worsens. Their preexisting geriatric conditions might be a moving target after another hit and another traumatic stressor like the ICU setting,” Dr. Cobert said.
The study by Dr. Cobert and colleagues was supported by the National Institute on Aging. Dr. Cobert had no reported conflicts of interest.
Baseball legend Leroy “Satchel” Paige famously said that “age is a question of mind over matter: If you don’t mind, it doesn’t matter.”
But even the strongest and most supple minds can’t avoid the effects of advanced age and accompanying physical frailty, and for community-dwelling elderly with pulmonary diseases frailty is a predictor of both hospitalization and death, investigators have found.
For example, among 1,188 community-dwelling older adults enrolled in the Toledo (Spain) Study for Healthy Aging, declining pulmonary function measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was associated with increased risk for frailty and hospitalization, and a more than twofold greater risk for death in participants both with and without respiratory diseases. These findings were reported by Walter Sepulveda-Loyola, PT, MSC, PhD, from the Faculty of Health and Social Sciences at Universidad de Las Americas in Santiago, Chile, and colleagues in the journal Heart & Lung.
Similarly, results of a meta-analysis performed by investigators at Jiangsu (China) University showed that among 13,203 patients with chronic obstructive pulmonary disease (COPD), frailty was associated with a more than 2.6-fold relative increase in risk for death from any cause, and “prefrailty,” an intermediate state between frailty and “robustness,” was associated with a 48% relative increase in all-cause mortality. Frailty was also associated with a 2.2-fold risk for COPD exacerbations of any severity, the authors reported in JAMDA: The Journal of Post-Acute and Long-Term Care Medicine.
The good (old) USA
In June 2023 the U.S. Census Bureau announced that the median age of the U.S. population is now 38.9 years, and according to a 2016 Census Bureau report funded by the National Institutes of Health, “America’s 65-and-over population is projected to nearly double over the next three decades, from 48 million to 88 million by 2050.”
With the graying of the U.S. population the burden on pulmonary and critical care experts will almost inevitably increase, as evidenced by research from Julien Cobert, MD, from the University of California, San Francisco, and colleagues.
The investigators looked at trends over time in older adults admitted to ICUs from 1988 through 2015 using data from the Health and Retirement Study (HRS), a nationally representative, longitudinal study of older adults. They found that rates of preexisting frailty, disability, and multimorbidity increased over the study period.
“Our findings suggest a growing prevalence of geriatric conditions among older adults admitted to the ICU, suggesting a pressing need to integrate geriatric principles into critical care medicine. Further research could examine if early interventions emphasizing physical, cognitive, mental health, delirium prevention, advance care planning, and rehabilitation individualized to critically ill elderly patients with preexisting geriatric conditions could improve ICU outcomes and post-ICU recovery,” they wrote in a study published in the journal CHEST.
In an editorial accompanying the study by Dr. Cobert and colleagues, Nathan E. Brummel, MD, from The Ohio State University College of Medicine and Davis Heart and Lung Research Institute in Columbus, said “the finding that nearly 30% of overall HRS participants were admitted to the ICU provides novel data about the extent to which older Americans are affected by critical illness. Because the number of older Americans is projected to continue to increase for the next 30 years or more, these data make clear the ongoing importance of aging-focused research and clinical care.”
Dr. Brummel also noted that older adults who are admitted to the ICU today are at greater risk for poor outcomes than those admitted in prior years, as evidenced by the increased prevalence of disability, frailty, and multimorbidity.
“Moreover, because the average age of those admitted to the ICU only changed by 1 year during the study, these data show that increases in vulnerability are not simply due to chronological age, and they suggest that to identify those with greater baseline vulnerability, screening for geriatric syndromes at ICU admission may be warranted,” he wrote.
Geriatric principles in the ICU
“I think what’s most important is that we think about patients from a geriatric principles standpoint, not just when they’re admitted to the hospital but especially when they’re admitted to the ICU,” Dr. Cobert said in an interview.
“The first step is ensuring that we’re asking questions about their underlying comorbidities, especially around frailty, hearing, vision loss, falls, multimorbidities, polypharmacy – things that are primarily done on the outpatient side in geriatric clinics, but things that we should probably be a little bit more cognizant of, given that we’re starting to see higher rates of patients coming in with these issues,” he said.
Critical care specialists need to take a more holistic approach and try to understand as best they can each patients’ goals and then determine whether the ICU staff are acting in concordance with those goals, he emphasized.
For example, ICU clinicians should try to understand whether patients were losing function or having mobility difficulties before hospital and ICU admission, and what they hope to retain when or if they are discharged. ICU staff can then try as much as reasonably possible to minimize interventions that could contribute to impairment after discharge.
Frailty and COPD in the ICU
There are special considerations for frail elderly with obstructive airway disease, Dr. Cobert noted.
Patients with advanced COPD, for example, are likely to be on home oxygen.
“Home oxygen is a big deal,” he said. “It can definitely help with functioning and there’s potentially a mortality benefit in certain populations. But that said, it’s a flammable object that they have to carry around and lug with them all the time. It contributes to falls, it’s tethering, it’s life-limiting in many ways.”
In addition, many patients with COPD have multiple re-hospitalizations, and for clinicians the challenge is “understanding what their goals are, what their motivations are, especially when they live with dyspnea, with advanced lung disease. Is intubation within their goals of care? Has their functional status been declining over time? Are there things that we can optimize holistically and globally as their COPD advances over time?”
Another important component of critical care for the frail elderly is consideration of patients’ palliative care needs and what their symptoms and symptom burdens were like prior to hospitalizations.
“The ICU experience and the critical illness experience may serve as an inflexion point – more likely a downward inflection point – whereby their needs increase, their symptoms can worsen, and their health, especially their global health, worsens. Their preexisting geriatric conditions might be a moving target after another hit and another traumatic stressor like the ICU setting,” Dr. Cobert said.
The study by Dr. Cobert and colleagues was supported by the National Institute on Aging. Dr. Cobert had no reported conflicts of interest.
Baseball legend Leroy “Satchel” Paige famously said that “age is a question of mind over matter: If you don’t mind, it doesn’t matter.”
But even the strongest and most supple minds can’t avoid the effects of advanced age and accompanying physical frailty, and for community-dwelling elderly with pulmonary diseases frailty is a predictor of both hospitalization and death, investigators have found.
For example, among 1,188 community-dwelling older adults enrolled in the Toledo (Spain) Study for Healthy Aging, declining pulmonary function measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was associated with increased risk for frailty and hospitalization, and a more than twofold greater risk for death in participants both with and without respiratory diseases. These findings were reported by Walter Sepulveda-Loyola, PT, MSC, PhD, from the Faculty of Health and Social Sciences at Universidad de Las Americas in Santiago, Chile, and colleagues in the journal Heart & Lung.
Similarly, results of a meta-analysis performed by investigators at Jiangsu (China) University showed that among 13,203 patients with chronic obstructive pulmonary disease (COPD), frailty was associated with a more than 2.6-fold relative increase in risk for death from any cause, and “prefrailty,” an intermediate state between frailty and “robustness,” was associated with a 48% relative increase in all-cause mortality. Frailty was also associated with a 2.2-fold risk for COPD exacerbations of any severity, the authors reported in JAMDA: The Journal of Post-Acute and Long-Term Care Medicine.
The good (old) USA
In June 2023 the U.S. Census Bureau announced that the median age of the U.S. population is now 38.9 years, and according to a 2016 Census Bureau report funded by the National Institutes of Health, “America’s 65-and-over population is projected to nearly double over the next three decades, from 48 million to 88 million by 2050.”
With the graying of the U.S. population the burden on pulmonary and critical care experts will almost inevitably increase, as evidenced by research from Julien Cobert, MD, from the University of California, San Francisco, and colleagues.
The investigators looked at trends over time in older adults admitted to ICUs from 1988 through 2015 using data from the Health and Retirement Study (HRS), a nationally representative, longitudinal study of older adults. They found that rates of preexisting frailty, disability, and multimorbidity increased over the study period.
“Our findings suggest a growing prevalence of geriatric conditions among older adults admitted to the ICU, suggesting a pressing need to integrate geriatric principles into critical care medicine. Further research could examine if early interventions emphasizing physical, cognitive, mental health, delirium prevention, advance care planning, and rehabilitation individualized to critically ill elderly patients with preexisting geriatric conditions could improve ICU outcomes and post-ICU recovery,” they wrote in a study published in the journal CHEST.
In an editorial accompanying the study by Dr. Cobert and colleagues, Nathan E. Brummel, MD, from The Ohio State University College of Medicine and Davis Heart and Lung Research Institute in Columbus, said “the finding that nearly 30% of overall HRS participants were admitted to the ICU provides novel data about the extent to which older Americans are affected by critical illness. Because the number of older Americans is projected to continue to increase for the next 30 years or more, these data make clear the ongoing importance of aging-focused research and clinical care.”
Dr. Brummel also noted that older adults who are admitted to the ICU today are at greater risk for poor outcomes than those admitted in prior years, as evidenced by the increased prevalence of disability, frailty, and multimorbidity.
“Moreover, because the average age of those admitted to the ICU only changed by 1 year during the study, these data show that increases in vulnerability are not simply due to chronological age, and they suggest that to identify those with greater baseline vulnerability, screening for geriatric syndromes at ICU admission may be warranted,” he wrote.
Geriatric principles in the ICU
“I think what’s most important is that we think about patients from a geriatric principles standpoint, not just when they’re admitted to the hospital but especially when they’re admitted to the ICU,” Dr. Cobert said in an interview.
“The first step is ensuring that we’re asking questions about their underlying comorbidities, especially around frailty, hearing, vision loss, falls, multimorbidities, polypharmacy – things that are primarily done on the outpatient side in geriatric clinics, but things that we should probably be a little bit more cognizant of, given that we’re starting to see higher rates of patients coming in with these issues,” he said.
Critical care specialists need to take a more holistic approach and try to understand as best they can each patients’ goals and then determine whether the ICU staff are acting in concordance with those goals, he emphasized.
For example, ICU clinicians should try to understand whether patients were losing function or having mobility difficulties before hospital and ICU admission, and what they hope to retain when or if they are discharged. ICU staff can then try as much as reasonably possible to minimize interventions that could contribute to impairment after discharge.
Frailty and COPD in the ICU
There are special considerations for frail elderly with obstructive airway disease, Dr. Cobert noted.
Patients with advanced COPD, for example, are likely to be on home oxygen.
“Home oxygen is a big deal,” he said. “It can definitely help with functioning and there’s potentially a mortality benefit in certain populations. But that said, it’s a flammable object that they have to carry around and lug with them all the time. It contributes to falls, it’s tethering, it’s life-limiting in many ways.”
In addition, many patients with COPD have multiple re-hospitalizations, and for clinicians the challenge is “understanding what their goals are, what their motivations are, especially when they live with dyspnea, with advanced lung disease. Is intubation within their goals of care? Has their functional status been declining over time? Are there things that we can optimize holistically and globally as their COPD advances over time?”
Another important component of critical care for the frail elderly is consideration of patients’ palliative care needs and what their symptoms and symptom burdens were like prior to hospitalizations.
“The ICU experience and the critical illness experience may serve as an inflexion point – more likely a downward inflection point – whereby their needs increase, their symptoms can worsen, and their health, especially their global health, worsens. Their preexisting geriatric conditions might be a moving target after another hit and another traumatic stressor like the ICU setting,” Dr. Cobert said.
The study by Dr. Cobert and colleagues was supported by the National Institute on Aging. Dr. Cobert had no reported conflicts of interest.