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Alectinib in ALK+ NSCLC is a watershed moment
CHICAGO – In what’s being hailed as practice-changing findings, the anaplastic lymphoma kinase inhibitor alectinib (Alecensa) was associated with more than doubled progression-free survival (PFS), compared with crizotinib (Xalkori), the current standard of care, in patients with treatment-naive non–small cell lung cancer (NSCLC) positive for ALK.
Additionally, in the global, phase III trial, alectinib was associated with a significantly lower risk of progression to CNS metastases, a common complication of advanced ALK+ NSCLC, reported Alice T. Shaw, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston, on behalf of investigators in the ALEX trial.
“I view this as a watershed moment for the treatment of ALK mutant–positive lung cancer,” commented ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
Unlike other head-to-head studies of similar drugs that frequently show only incremental benefit, the ALEX results showed a dramatic difference in outcomes for patients treated with alectinib, he said.
By comparison, the median PFS difference between chemotherapy and crizotinib in the PROFILE 1014 in patients with ALK-positive NSCLC trial was 10.9 vs. 7.0 months, Dr. Heymach pointed out.
The ALEX investigators enrolled 303 patients with untreated ALK-positive NSCLC confirmed by a central immunohistochemistry lab and randomly assigned them to treatment with either oral alectinib 600 mg twice daily or crizotinib 250 mg b.i.d.
At the primary data cutoff in February 2017, median PFS, the primary endpoint, was 11.1 months for patients treated with crizotinib, versus not reached for those treated with alectinib, translating into a hazard ratio for alectinib of 0.47 (P less than .0001).
Based on an independent review, the median PFS was determined to be 10.4 months for crizotinib, vs. 25.7 months with alectinib (HR, 0.50; P not shown).
The cumulative incidence of CNS progression, a secondary endpoint, was 41.4% in the crizotinib arm, vs. 9.41% in the alectinib arm (cause-specific HR, 0.16; P not shown).
In each arm, 97% of patients had any adverse event, and the incidence of serious adverse events was similar between the arms, at 29% for crizotinib and 28% for alectinib.
Adverse events leading to treatment discontinuation, dose reduction, or dose interruption were more frequent with crizotinib.
In the question and answer portion of the briefing, Dr. Shaw was asked whether crizotinib still had a role in this population.
“Going forward, I think that it’s pretty clear, if you have a newly diagnosed patient with metastatic ALK-positive lung cancer, that likely alectinib would be the preferred first choice,” she said.
The ALEX trial is supported by Roche. Dr. Shaw disclosed consulting or an advisory role with the company, and multiple coauthors disclosed similar relationships.
CHICAGO – In what’s being hailed as practice-changing findings, the anaplastic lymphoma kinase inhibitor alectinib (Alecensa) was associated with more than doubled progression-free survival (PFS), compared with crizotinib (Xalkori), the current standard of care, in patients with treatment-naive non–small cell lung cancer (NSCLC) positive for ALK.
Additionally, in the global, phase III trial, alectinib was associated with a significantly lower risk of progression to CNS metastases, a common complication of advanced ALK+ NSCLC, reported Alice T. Shaw, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston, on behalf of investigators in the ALEX trial.
“I view this as a watershed moment for the treatment of ALK mutant–positive lung cancer,” commented ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
Unlike other head-to-head studies of similar drugs that frequently show only incremental benefit, the ALEX results showed a dramatic difference in outcomes for patients treated with alectinib, he said.
By comparison, the median PFS difference between chemotherapy and crizotinib in the PROFILE 1014 in patients with ALK-positive NSCLC trial was 10.9 vs. 7.0 months, Dr. Heymach pointed out.
The ALEX investigators enrolled 303 patients with untreated ALK-positive NSCLC confirmed by a central immunohistochemistry lab and randomly assigned them to treatment with either oral alectinib 600 mg twice daily or crizotinib 250 mg b.i.d.
At the primary data cutoff in February 2017, median PFS, the primary endpoint, was 11.1 months for patients treated with crizotinib, versus not reached for those treated with alectinib, translating into a hazard ratio for alectinib of 0.47 (P less than .0001).
Based on an independent review, the median PFS was determined to be 10.4 months for crizotinib, vs. 25.7 months with alectinib (HR, 0.50; P not shown).
The cumulative incidence of CNS progression, a secondary endpoint, was 41.4% in the crizotinib arm, vs. 9.41% in the alectinib arm (cause-specific HR, 0.16; P not shown).
In each arm, 97% of patients had any adverse event, and the incidence of serious adverse events was similar between the arms, at 29% for crizotinib and 28% for alectinib.
Adverse events leading to treatment discontinuation, dose reduction, or dose interruption were more frequent with crizotinib.
In the question and answer portion of the briefing, Dr. Shaw was asked whether crizotinib still had a role in this population.
“Going forward, I think that it’s pretty clear, if you have a newly diagnosed patient with metastatic ALK-positive lung cancer, that likely alectinib would be the preferred first choice,” she said.
The ALEX trial is supported by Roche. Dr. Shaw disclosed consulting or an advisory role with the company, and multiple coauthors disclosed similar relationships.
CHICAGO – In what’s being hailed as practice-changing findings, the anaplastic lymphoma kinase inhibitor alectinib (Alecensa) was associated with more than doubled progression-free survival (PFS), compared with crizotinib (Xalkori), the current standard of care, in patients with treatment-naive non–small cell lung cancer (NSCLC) positive for ALK.
Additionally, in the global, phase III trial, alectinib was associated with a significantly lower risk of progression to CNS metastases, a common complication of advanced ALK+ NSCLC, reported Alice T. Shaw, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston, on behalf of investigators in the ALEX trial.
“I view this as a watershed moment for the treatment of ALK mutant–positive lung cancer,” commented ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
Unlike other head-to-head studies of similar drugs that frequently show only incremental benefit, the ALEX results showed a dramatic difference in outcomes for patients treated with alectinib, he said.
By comparison, the median PFS difference between chemotherapy and crizotinib in the PROFILE 1014 in patients with ALK-positive NSCLC trial was 10.9 vs. 7.0 months, Dr. Heymach pointed out.
The ALEX investigators enrolled 303 patients with untreated ALK-positive NSCLC confirmed by a central immunohistochemistry lab and randomly assigned them to treatment with either oral alectinib 600 mg twice daily or crizotinib 250 mg b.i.d.
At the primary data cutoff in February 2017, median PFS, the primary endpoint, was 11.1 months for patients treated with crizotinib, versus not reached for those treated with alectinib, translating into a hazard ratio for alectinib of 0.47 (P less than .0001).
Based on an independent review, the median PFS was determined to be 10.4 months for crizotinib, vs. 25.7 months with alectinib (HR, 0.50; P not shown).
The cumulative incidence of CNS progression, a secondary endpoint, was 41.4% in the crizotinib arm, vs. 9.41% in the alectinib arm (cause-specific HR, 0.16; P not shown).
In each arm, 97% of patients had any adverse event, and the incidence of serious adverse events was similar between the arms, at 29% for crizotinib and 28% for alectinib.
Adverse events leading to treatment discontinuation, dose reduction, or dose interruption were more frequent with crizotinib.
In the question and answer portion of the briefing, Dr. Shaw was asked whether crizotinib still had a role in this population.
“Going forward, I think that it’s pretty clear, if you have a newly diagnosed patient with metastatic ALK-positive lung cancer, that likely alectinib would be the preferred first choice,” she said.
The ALEX trial is supported by Roche. Dr. Shaw disclosed consulting or an advisory role with the company, and multiple coauthors disclosed similar relationships.
AT ASCO 2017
Key clinical point: Alectinib was associated with more than double the progression-free survival of standard of care crizotinib in patients with non–small cell lung cancer positive for the anaplastic lymphoma kinase.
Major finding: Median PFS by independent review was 10.4 months with crizotinib vs. 25.7 months with alectinib.
Data source: The ALEX trial, a phase III trial of 303 patients with ALK-positive NSCLC.
Disclosures: The ALEX trial is supported by Roche. Dr. Shaw disclosed consulting or an advisory role with the company, and multiple coauthors disclosed similar relationships
Persistently nondysplastic Barrett’s esophagus did not protect against progression
Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).
The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.
Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.
A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.
The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.
The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.
The investigators did not report funding sources. They reported having no conflicts of interest.
Current practice guidelines recommend endoscopic surveillance in Barrett’s esophagus (BE) patients to detect esophageal adenocarcinoma (EAC) at an early and potentially curable stage.
As currently practiced, endoscopic surveillance of BE has numerous limitations and provides the impetus for improved risk-stratification and, ultimately, the effectiveness of current surveillance strategies. Persistence of nondysplastic BE (NDBE) has previously been shown to be an indicator of lower risk of progression to high-grade dysplasia (HGD)/EAC. However, outcomes studies on this topic have reported conflicting results.
Where do we stand with regard to persistence of NDBE and its impact on surveillance intervals? Future large cohort studies are required that address all potential confounders and include a large number of patients with progression to HGD/EAC (a challenge given the rarity of this outcome). At the present time, based on the available data, surveillance intervals cannot be lengthened in patients with persistent NDBE. Future studies also need to focus on the development and validation of prediction models that incorporate clinical, endoscopic, and histologic factors in risk stratification. Until then, meticulous examination techniques, cognitive knowledge and training, use of standardized grading systems, and use of high-definition white light endoscopy are critical in improving effectiveness of surveillance programs in BE patients.
Sachin Wani, MD, is associate professor of medicine and Medical codirector of the Esophageal and Gastric Center of Excellence, division of gastroenterology and hepatology, University of Colorado at Denver, Aurora. He is supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program and is a consultant for Medtronic and Boston Scientific.
Current practice guidelines recommend endoscopic surveillance in Barrett’s esophagus (BE) patients to detect esophageal adenocarcinoma (EAC) at an early and potentially curable stage.
As currently practiced, endoscopic surveillance of BE has numerous limitations and provides the impetus for improved risk-stratification and, ultimately, the effectiveness of current surveillance strategies. Persistence of nondysplastic BE (NDBE) has previously been shown to be an indicator of lower risk of progression to high-grade dysplasia (HGD)/EAC. However, outcomes studies on this topic have reported conflicting results.
Where do we stand with regard to persistence of NDBE and its impact on surveillance intervals? Future large cohort studies are required that address all potential confounders and include a large number of patients with progression to HGD/EAC (a challenge given the rarity of this outcome). At the present time, based on the available data, surveillance intervals cannot be lengthened in patients with persistent NDBE. Future studies also need to focus on the development and validation of prediction models that incorporate clinical, endoscopic, and histologic factors in risk stratification. Until then, meticulous examination techniques, cognitive knowledge and training, use of standardized grading systems, and use of high-definition white light endoscopy are critical in improving effectiveness of surveillance programs in BE patients.
Sachin Wani, MD, is associate professor of medicine and Medical codirector of the Esophageal and Gastric Center of Excellence, division of gastroenterology and hepatology, University of Colorado at Denver, Aurora. He is supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program and is a consultant for Medtronic and Boston Scientific.
Current practice guidelines recommend endoscopic surveillance in Barrett’s esophagus (BE) patients to detect esophageal adenocarcinoma (EAC) at an early and potentially curable stage.
As currently practiced, endoscopic surveillance of BE has numerous limitations and provides the impetus for improved risk-stratification and, ultimately, the effectiveness of current surveillance strategies. Persistence of nondysplastic BE (NDBE) has previously been shown to be an indicator of lower risk of progression to high-grade dysplasia (HGD)/EAC. However, outcomes studies on this topic have reported conflicting results.
Where do we stand with regard to persistence of NDBE and its impact on surveillance intervals? Future large cohort studies are required that address all potential confounders and include a large number of patients with progression to HGD/EAC (a challenge given the rarity of this outcome). At the present time, based on the available data, surveillance intervals cannot be lengthened in patients with persistent NDBE. Future studies also need to focus on the development and validation of prediction models that incorporate clinical, endoscopic, and histologic factors in risk stratification. Until then, meticulous examination techniques, cognitive knowledge and training, use of standardized grading systems, and use of high-definition white light endoscopy are critical in improving effectiveness of surveillance programs in BE patients.
Sachin Wani, MD, is associate professor of medicine and Medical codirector of the Esophageal and Gastric Center of Excellence, division of gastroenterology and hepatology, University of Colorado at Denver, Aurora. He is supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program and is a consultant for Medtronic and Boston Scientific.
Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).
The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.
Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.
A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.
The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.
The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.
The investigators did not report funding sources. They reported having no conflicts of interest.
Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).
The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.
Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.
A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.
The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.
The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.
The investigators did not report funding sources. They reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Patients with multiple consecutive biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to esophageal adenocarcinoma or high-grade dysplasia as those with a single nondysplastic biopsy.
Major finding: Hazard ratios for progression ranged between 0.00 and 0.85, with no significant difference in estimated risk among groups stratified by number of consecutive nondysplastic biopsies (P = .68), after controlling for age, sex, and length of Barrett’s esophagus.
Data source: A prospective multicenter registry of 480 patients with nondysplastic Barrett’s esophagus and multiple surveillance biopsies.
Disclosures: The investigators did not report funding sources. They reported having no conflicts of interest.
Study: Antibiotic monotherapy fails 25% of CAP patients
WASHINGTON – A substantial failure rate of antibiotic monotherapy was found in patients with community acquired pneumonia (CAP), according to a presentation given at an international conference of the American Thoracic Society.
In a study of 413,801 patient records with confirmed CAP, an average of 25% of patients reported treatment failure, according to James A McKinnell, MD, an infectious disease specialist at LA BioMed and an assistant professor at the University of California, Los Angeles.
Adult outpatient records with a diagnosis of CAP and a prescription for antibiotics were gathered from the period of 2012-2015, with treatment failure defined as a refill or change in the medication prescribed, a visit to the emergency department, or a hospitalization, according to Dr. McKinnell and the other investigators.
When broken down, the failure rates in patients given beta-lactams (25.7%), macrolides (22.9%), tetracycline (22.5%), and fluoroquinolones (20.8%), were all found to increase when patients’ Charlson Comorbidity Index (CCI) score increased (odds ration [OR] = 1.16 [1.13-1.20] for CCI = 1, OR = 1.22 [1.18-1.26], for CCI = 2, OR = 1.44 [1.39-1.49], for CCI greater than or equal to 3).
These medications have been shown to be effective through the usual array of controlled tests. While these trials do confirm overall efficacy, they are not always accurate in predicting how they will affect individual patients, Dr. McKinnell noted.
“I want to know the best drug for my patient, [and] unfortunately randomized clinical trials are not completely generalizable,” Dr. McKinnell said during his presentation. “Pathogen distribution and resistance is different in a clinical trial compared to the patients we see, and there’s a measuring bias, so there’s a lot of limitations when just using clinical trials.”
When analyzing failure endpoints, the investigators found 79%, 73.4%, 80.8%, and 64% of patients switched their antibiotics while taking beta-lactams, macrolides, tetracycline, or fluoroquinolones, respectively. The investigators interpreted this as a sign that patient treatment plans must be better fitted for their personal circumstances.
This is where the idea of “big data” would apply; using large-scale, “real-world” data of current and previous CAP patients could be instrumental to test the benefits and limitations of certain treatment options on patients with certain comorbidities, according to Dr. McKinnell and his fellow investigators.
When breaking down comorbidities among patients, the investigators found that many of the comorbid conditions had a “significant predictor value” of treatment failure, according to Dr. McKinnell.
Investigators were not surprised that hemiplegia or paraplegia, which increased the odds of antibiotic failure by 33%, were independent factors; however, comorbidities such as peptic ulcer disease (OR: 1.15) was less expected, Dr. McKinnell noted.
When looking at the mortality rate of patients 18 years of age and older with treatment failure, 18.1% (10,087) died (P less than .0001), with an even higher mortality rate of 24.3% (3,299) among those at least 65 years of age, he said.
If big data studies could decrease the number of treatment failures, the implications would be significant in decreasing the number of mortalities, the investigators noted.
“Prescribers should be aware of those CAP patients most at risk for poor outcomes and consider these factors to guide a comprehensive treatment plan,” said Dr. McKinnell.
Cempra Pharmaceuticals funded the study. The researchers did not report any conflicts of interest during their presentation.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – A substantial failure rate of antibiotic monotherapy was found in patients with community acquired pneumonia (CAP), according to a presentation given at an international conference of the American Thoracic Society.
In a study of 413,801 patient records with confirmed CAP, an average of 25% of patients reported treatment failure, according to James A McKinnell, MD, an infectious disease specialist at LA BioMed and an assistant professor at the University of California, Los Angeles.
Adult outpatient records with a diagnosis of CAP and a prescription for antibiotics were gathered from the period of 2012-2015, with treatment failure defined as a refill or change in the medication prescribed, a visit to the emergency department, or a hospitalization, according to Dr. McKinnell and the other investigators.
When broken down, the failure rates in patients given beta-lactams (25.7%), macrolides (22.9%), tetracycline (22.5%), and fluoroquinolones (20.8%), were all found to increase when patients’ Charlson Comorbidity Index (CCI) score increased (odds ration [OR] = 1.16 [1.13-1.20] for CCI = 1, OR = 1.22 [1.18-1.26], for CCI = 2, OR = 1.44 [1.39-1.49], for CCI greater than or equal to 3).
These medications have been shown to be effective through the usual array of controlled tests. While these trials do confirm overall efficacy, they are not always accurate in predicting how they will affect individual patients, Dr. McKinnell noted.
“I want to know the best drug for my patient, [and] unfortunately randomized clinical trials are not completely generalizable,” Dr. McKinnell said during his presentation. “Pathogen distribution and resistance is different in a clinical trial compared to the patients we see, and there’s a measuring bias, so there’s a lot of limitations when just using clinical trials.”
When analyzing failure endpoints, the investigators found 79%, 73.4%, 80.8%, and 64% of patients switched their antibiotics while taking beta-lactams, macrolides, tetracycline, or fluoroquinolones, respectively. The investigators interpreted this as a sign that patient treatment plans must be better fitted for their personal circumstances.
This is where the idea of “big data” would apply; using large-scale, “real-world” data of current and previous CAP patients could be instrumental to test the benefits and limitations of certain treatment options on patients with certain comorbidities, according to Dr. McKinnell and his fellow investigators.
When breaking down comorbidities among patients, the investigators found that many of the comorbid conditions had a “significant predictor value” of treatment failure, according to Dr. McKinnell.
Investigators were not surprised that hemiplegia or paraplegia, which increased the odds of antibiotic failure by 33%, were independent factors; however, comorbidities such as peptic ulcer disease (OR: 1.15) was less expected, Dr. McKinnell noted.
When looking at the mortality rate of patients 18 years of age and older with treatment failure, 18.1% (10,087) died (P less than .0001), with an even higher mortality rate of 24.3% (3,299) among those at least 65 years of age, he said.
If big data studies could decrease the number of treatment failures, the implications would be significant in decreasing the number of mortalities, the investigators noted.
“Prescribers should be aware of those CAP patients most at risk for poor outcomes and consider these factors to guide a comprehensive treatment plan,” said Dr. McKinnell.
Cempra Pharmaceuticals funded the study. The researchers did not report any conflicts of interest during their presentation.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – A substantial failure rate of antibiotic monotherapy was found in patients with community acquired pneumonia (CAP), according to a presentation given at an international conference of the American Thoracic Society.
In a study of 413,801 patient records with confirmed CAP, an average of 25% of patients reported treatment failure, according to James A McKinnell, MD, an infectious disease specialist at LA BioMed and an assistant professor at the University of California, Los Angeles.
Adult outpatient records with a diagnosis of CAP and a prescription for antibiotics were gathered from the period of 2012-2015, with treatment failure defined as a refill or change in the medication prescribed, a visit to the emergency department, or a hospitalization, according to Dr. McKinnell and the other investigators.
When broken down, the failure rates in patients given beta-lactams (25.7%), macrolides (22.9%), tetracycline (22.5%), and fluoroquinolones (20.8%), were all found to increase when patients’ Charlson Comorbidity Index (CCI) score increased (odds ration [OR] = 1.16 [1.13-1.20] for CCI = 1, OR = 1.22 [1.18-1.26], for CCI = 2, OR = 1.44 [1.39-1.49], for CCI greater than or equal to 3).
These medications have been shown to be effective through the usual array of controlled tests. While these trials do confirm overall efficacy, they are not always accurate in predicting how they will affect individual patients, Dr. McKinnell noted.
“I want to know the best drug for my patient, [and] unfortunately randomized clinical trials are not completely generalizable,” Dr. McKinnell said during his presentation. “Pathogen distribution and resistance is different in a clinical trial compared to the patients we see, and there’s a measuring bias, so there’s a lot of limitations when just using clinical trials.”
When analyzing failure endpoints, the investigators found 79%, 73.4%, 80.8%, and 64% of patients switched their antibiotics while taking beta-lactams, macrolides, tetracycline, or fluoroquinolones, respectively. The investigators interpreted this as a sign that patient treatment plans must be better fitted for their personal circumstances.
This is where the idea of “big data” would apply; using large-scale, “real-world” data of current and previous CAP patients could be instrumental to test the benefits and limitations of certain treatment options on patients with certain comorbidities, according to Dr. McKinnell and his fellow investigators.
When breaking down comorbidities among patients, the investigators found that many of the comorbid conditions had a “significant predictor value” of treatment failure, according to Dr. McKinnell.
Investigators were not surprised that hemiplegia or paraplegia, which increased the odds of antibiotic failure by 33%, were independent factors; however, comorbidities such as peptic ulcer disease (OR: 1.15) was less expected, Dr. McKinnell noted.
When looking at the mortality rate of patients 18 years of age and older with treatment failure, 18.1% (10,087) died (P less than .0001), with an even higher mortality rate of 24.3% (3,299) among those at least 65 years of age, he said.
If big data studies could decrease the number of treatment failures, the implications would be significant in decreasing the number of mortalities, the investigators noted.
“Prescribers should be aware of those CAP patients most at risk for poor outcomes and consider these factors to guide a comprehensive treatment plan,” said Dr. McKinnell.
Cempra Pharmaceuticals funded the study. The researchers did not report any conflicts of interest during their presentation.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM ATS 2017
Key clinical point:
Major finding: On average, 25% of patients experienced treatment failure for antibiotic monotherapy, which was exacerbated by increasing Charlson comorbidity index scores (OR = 1.16 [1.13-1.20] for CCI = 1, OR = 1.22 [1.18-1.26] for CCI = 2, OR = 1.44 [1.39-1.49] for CCI greater than or equal to 3).
Data source: Retrospective study of 413,801 patients with CAP gathered from the commercial claims encounters database and the Medicare supplemental coordination benefits database between January 2011 and December 2015.
Disclosures: Cempra Pharmaceuticals funded the study. The researchers did not report any conflicts of interest during their presentation.
VIDEO: Wedge resection offers higher survival for NSCLC
BOSTON – High quality wedge resection results in higher survival for patients with early stage non–small cell lung cancer when compared with stereotactic body radiation therapy, according to new research.
The analysis, reported at the annual meeting of the American Association for Thoracic Surgery, evaluated the treatment of 7,337 patients in the National Cancer Database with clinical T1-T2, N0, M0 non–small cell lung cancer who were treated with either wedge resection or stereotactic body radiation therapy from 2005 to 2012.
In this video, Varun Puri, MD, of Washington University, St. Louis, discusses the study and the significance of the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
agallegos@frontlinemedcom.com
On Twitter @legal_med
BOSTON – High quality wedge resection results in higher survival for patients with early stage non–small cell lung cancer when compared with stereotactic body radiation therapy, according to new research.
The analysis, reported at the annual meeting of the American Association for Thoracic Surgery, evaluated the treatment of 7,337 patients in the National Cancer Database with clinical T1-T2, N0, M0 non–small cell lung cancer who were treated with either wedge resection or stereotactic body radiation therapy from 2005 to 2012.
In this video, Varun Puri, MD, of Washington University, St. Louis, discusses the study and the significance of the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
agallegos@frontlinemedcom.com
On Twitter @legal_med
BOSTON – High quality wedge resection results in higher survival for patients with early stage non–small cell lung cancer when compared with stereotactic body radiation therapy, according to new research.
The analysis, reported at the annual meeting of the American Association for Thoracic Surgery, evaluated the treatment of 7,337 patients in the National Cancer Database with clinical T1-T2, N0, M0 non–small cell lung cancer who were treated with either wedge resection or stereotactic body radiation therapy from 2005 to 2012.
In this video, Varun Puri, MD, of Washington University, St. Louis, discusses the study and the significance of the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
agallegos@frontlinemedcom.com
On Twitter @legal_med
AT THE AATS ANNUAL MEETING
VIDEO: Lack of heart teams impact prevalence of PCI
BOSTON – Data show a marked bias in referral patterns for coronary revascularization in stand-alone interventional cardiology units lacking a heart team.
More patients underwent percutaneous coronary intervention (PCI) in hospitals without on-site cardiac surgery than patients at hospitals with on-site cardiac surgery, according to the analysis presented at the annual meeting of the American Association for Thoracic Surgery. The multivariate logistic regression analysis showed that the absence of on-site cardiac surgery and a heart team was an independent predictor for PCI.
In this video, Ehud Raanani, MD, of Tel Aviv University in Israel discusses referral patterns for coronary revascularization in stand-alone interventional cardiology units lacking a heart team and how this phenomenon could affect patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
agallegos@frontlinemedcom.com
On Twitter @legal_med
BOSTON – Data show a marked bias in referral patterns for coronary revascularization in stand-alone interventional cardiology units lacking a heart team.
More patients underwent percutaneous coronary intervention (PCI) in hospitals without on-site cardiac surgery than patients at hospitals with on-site cardiac surgery, according to the analysis presented at the annual meeting of the American Association for Thoracic Surgery. The multivariate logistic regression analysis showed that the absence of on-site cardiac surgery and a heart team was an independent predictor for PCI.
In this video, Ehud Raanani, MD, of Tel Aviv University in Israel discusses referral patterns for coronary revascularization in stand-alone interventional cardiology units lacking a heart team and how this phenomenon could affect patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
agallegos@frontlinemedcom.com
On Twitter @legal_med
BOSTON – Data show a marked bias in referral patterns for coronary revascularization in stand-alone interventional cardiology units lacking a heart team.
More patients underwent percutaneous coronary intervention (PCI) in hospitals without on-site cardiac surgery than patients at hospitals with on-site cardiac surgery, according to the analysis presented at the annual meeting of the American Association for Thoracic Surgery. The multivariate logistic regression analysis showed that the absence of on-site cardiac surgery and a heart team was an independent predictor for PCI.
In this video, Ehud Raanani, MD, of Tel Aviv University in Israel discusses referral patterns for coronary revascularization in stand-alone interventional cardiology units lacking a heart team and how this phenomenon could affect patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
agallegos@frontlinemedcom.com
On Twitter @legal_med
AT THE AATS ANNUAL MEETING
Gefitinib bests chemo as adjuvant therapy for early EGFR-mutant NSCLC
The targeted agent gefitinib is superior to the standard of care chemotherapy for treating resected early non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, finds the phase III randomized Chinese ADJUVANT trial.
Gefitinib, an oral tyrosine kinase inhibitor that targets the EGFR kinase among others, is already approved by the Food and Drug Administration for treatment of locally advanced or metastatic disease having mutations in the gene for this receptor.
Trial results reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology showed that compared with vinorelbine and cisplatin combination chemotherapy, 2 years of gefitinib prolonged the time to recurrence or death by more than 10 months, reducing risk of these events by a significant 40%. Gefitinib also was better tolerated: The rate of grade 3 or worse adverse events with the targeted agent was one-fourth that seen with the chemotherapy.
“Targeted therapy can delay recurrence of intermediate-stage lung cancer after surgery. Two-year treatment duration of gefitinib is efficacious and tolerated well,” said lead study author Yi-Long Wu, MD, director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. “Adjuvant gefitinib should be considered as an important option for stage II to IIIA lung cancer patients with an activating EGFR mutation.”
Clinical implications
The improved disease-free survival seen with gefitinib in ADJUVANT is “encouraging,” according to ASCO President-Elect Bruce E. Johnson, MD, chief clinical research officer and an Institute Physician at the Dana-Farber Cancer Institute in Boston.
Longer follow-up will be needed to obtain a full picture as the horizon for events in the adjuvant setting is more on the order of years, and the disease-free survival curves began converging over time, he noted. “We will ultimately be interested in seeing whether this actually prolongs survival in a longer follow-up study, which Dr. Wu’s group is planning to do.
“I haven’t changed my approach yet for the patients with EGFR-mutant lung cancer,” Dr. Johnson concluded. “But I will be following this [trial] very closely to see what happens to the survival.”
The new data from ADJUVANT will likely have several effects on the clinical management of NSCLC, according to presscast moderator and ASCO Chief Medical Officer Richard L. Schilsky, MD.
“I suspect that many doctors will begin testing these lung cancer tumors right after surgery, to see if they actually have an EGFR mutation. That is not currently standard of care in the U.S.; typically the testing doesn’t take place until the cancer recurs or becomes metastatic,” he said. “So that way, doctors and patients will know whether or not treatment with an EGFR inhibitor is even an option.
“If it is an option, then many factors will likely come into play, and most importantly we will be waiting for the survival data,” said Dr. Schilsky, professor emeritus at the University of Chicago. Another consideration is that the trial compared 12 weeks of chemotherapy with 2 years of continuous gefitinib therapy, the latter of which requires a long-term commitment to adherence by patients and carries much greater cost.
“At the end of the day, I think that once the survival data is known in particular, doctors and patients are going to have to have very thoughtful discussions about what is the magnitude of the survival benefit; what is the burden on the patient to take either cytotoxic chemotherapy for 12 weeks or 2 years of an oral treatment, which, while it is less toxic, is not without toxicity; and what’s the financial burden of that treatment choice going to be for the patient,” he concluded.
Study details
Eligibility for the ADJUVANT trial required completely resected pathological stage II-IIIA (N1-N2) NSCLC with an EGFR-activating mutation. In all, 220 patients were randomized evenly to receive gefitinib (Iressa) once daily for 24 months or vinorelbine plus cisplatin every 3 weeks for 4 cycles.
Results showed that median disease-free survival – the trial’s primary endpoint—was 28.7 months with gefitinib compared with 18.0 months with chemotherapy (hazard ratio, 0.60; P = .005), Dr. Wu reported in the presscast. Corresponding 3-year disease-free survival rates were 34% and 27%.
The rate of grade 3 or worse adverse events was 12.3% in the gefitinib group, compared with 48.3% in the chemotherapy group. Most types of events were less common with the tyrosine kinase inhibitor, with the exception of rash, diarrhea, and elevation of liver enzymes.
Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
The targeted agent gefitinib is superior to the standard of care chemotherapy for treating resected early non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, finds the phase III randomized Chinese ADJUVANT trial.
Gefitinib, an oral tyrosine kinase inhibitor that targets the EGFR kinase among others, is already approved by the Food and Drug Administration for treatment of locally advanced or metastatic disease having mutations in the gene for this receptor.
Trial results reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology showed that compared with vinorelbine and cisplatin combination chemotherapy, 2 years of gefitinib prolonged the time to recurrence or death by more than 10 months, reducing risk of these events by a significant 40%. Gefitinib also was better tolerated: The rate of grade 3 or worse adverse events with the targeted agent was one-fourth that seen with the chemotherapy.
“Targeted therapy can delay recurrence of intermediate-stage lung cancer after surgery. Two-year treatment duration of gefitinib is efficacious and tolerated well,” said lead study author Yi-Long Wu, MD, director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. “Adjuvant gefitinib should be considered as an important option for stage II to IIIA lung cancer patients with an activating EGFR mutation.”
Clinical implications
The improved disease-free survival seen with gefitinib in ADJUVANT is “encouraging,” according to ASCO President-Elect Bruce E. Johnson, MD, chief clinical research officer and an Institute Physician at the Dana-Farber Cancer Institute in Boston.
Longer follow-up will be needed to obtain a full picture as the horizon for events in the adjuvant setting is more on the order of years, and the disease-free survival curves began converging over time, he noted. “We will ultimately be interested in seeing whether this actually prolongs survival in a longer follow-up study, which Dr. Wu’s group is planning to do.
“I haven’t changed my approach yet for the patients with EGFR-mutant lung cancer,” Dr. Johnson concluded. “But I will be following this [trial] very closely to see what happens to the survival.”
The new data from ADJUVANT will likely have several effects on the clinical management of NSCLC, according to presscast moderator and ASCO Chief Medical Officer Richard L. Schilsky, MD.
“I suspect that many doctors will begin testing these lung cancer tumors right after surgery, to see if they actually have an EGFR mutation. That is not currently standard of care in the U.S.; typically the testing doesn’t take place until the cancer recurs or becomes metastatic,” he said. “So that way, doctors and patients will know whether or not treatment with an EGFR inhibitor is even an option.
“If it is an option, then many factors will likely come into play, and most importantly we will be waiting for the survival data,” said Dr. Schilsky, professor emeritus at the University of Chicago. Another consideration is that the trial compared 12 weeks of chemotherapy with 2 years of continuous gefitinib therapy, the latter of which requires a long-term commitment to adherence by patients and carries much greater cost.
“At the end of the day, I think that once the survival data is known in particular, doctors and patients are going to have to have very thoughtful discussions about what is the magnitude of the survival benefit; what is the burden on the patient to take either cytotoxic chemotherapy for 12 weeks or 2 years of an oral treatment, which, while it is less toxic, is not without toxicity; and what’s the financial burden of that treatment choice going to be for the patient,” he concluded.
Study details
Eligibility for the ADJUVANT trial required completely resected pathological stage II-IIIA (N1-N2) NSCLC with an EGFR-activating mutation. In all, 220 patients were randomized evenly to receive gefitinib (Iressa) once daily for 24 months or vinorelbine plus cisplatin every 3 weeks for 4 cycles.
Results showed that median disease-free survival – the trial’s primary endpoint—was 28.7 months with gefitinib compared with 18.0 months with chemotherapy (hazard ratio, 0.60; P = .005), Dr. Wu reported in the presscast. Corresponding 3-year disease-free survival rates were 34% and 27%.
The rate of grade 3 or worse adverse events was 12.3% in the gefitinib group, compared with 48.3% in the chemotherapy group. Most types of events were less common with the tyrosine kinase inhibitor, with the exception of rash, diarrhea, and elevation of liver enzymes.
Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
The targeted agent gefitinib is superior to the standard of care chemotherapy for treating resected early non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, finds the phase III randomized Chinese ADJUVANT trial.
Gefitinib, an oral tyrosine kinase inhibitor that targets the EGFR kinase among others, is already approved by the Food and Drug Administration for treatment of locally advanced or metastatic disease having mutations in the gene for this receptor.
Trial results reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology showed that compared with vinorelbine and cisplatin combination chemotherapy, 2 years of gefitinib prolonged the time to recurrence or death by more than 10 months, reducing risk of these events by a significant 40%. Gefitinib also was better tolerated: The rate of grade 3 or worse adverse events with the targeted agent was one-fourth that seen with the chemotherapy.
“Targeted therapy can delay recurrence of intermediate-stage lung cancer after surgery. Two-year treatment duration of gefitinib is efficacious and tolerated well,” said lead study author Yi-Long Wu, MD, director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. “Adjuvant gefitinib should be considered as an important option for stage II to IIIA lung cancer patients with an activating EGFR mutation.”
Clinical implications
The improved disease-free survival seen with gefitinib in ADJUVANT is “encouraging,” according to ASCO President-Elect Bruce E. Johnson, MD, chief clinical research officer and an Institute Physician at the Dana-Farber Cancer Institute in Boston.
Longer follow-up will be needed to obtain a full picture as the horizon for events in the adjuvant setting is more on the order of years, and the disease-free survival curves began converging over time, he noted. “We will ultimately be interested in seeing whether this actually prolongs survival in a longer follow-up study, which Dr. Wu’s group is planning to do.
“I haven’t changed my approach yet for the patients with EGFR-mutant lung cancer,” Dr. Johnson concluded. “But I will be following this [trial] very closely to see what happens to the survival.”
The new data from ADJUVANT will likely have several effects on the clinical management of NSCLC, according to presscast moderator and ASCO Chief Medical Officer Richard L. Schilsky, MD.
“I suspect that many doctors will begin testing these lung cancer tumors right after surgery, to see if they actually have an EGFR mutation. That is not currently standard of care in the U.S.; typically the testing doesn’t take place until the cancer recurs or becomes metastatic,” he said. “So that way, doctors and patients will know whether or not treatment with an EGFR inhibitor is even an option.
“If it is an option, then many factors will likely come into play, and most importantly we will be waiting for the survival data,” said Dr. Schilsky, professor emeritus at the University of Chicago. Another consideration is that the trial compared 12 weeks of chemotherapy with 2 years of continuous gefitinib therapy, the latter of which requires a long-term commitment to adherence by patients and carries much greater cost.
“At the end of the day, I think that once the survival data is known in particular, doctors and patients are going to have to have very thoughtful discussions about what is the magnitude of the survival benefit; what is the burden on the patient to take either cytotoxic chemotherapy for 12 weeks or 2 years of an oral treatment, which, while it is less toxic, is not without toxicity; and what’s the financial burden of that treatment choice going to be for the patient,” he concluded.
Study details
Eligibility for the ADJUVANT trial required completely resected pathological stage II-IIIA (N1-N2) NSCLC with an EGFR-activating mutation. In all, 220 patients were randomized evenly to receive gefitinib (Iressa) once daily for 24 months or vinorelbine plus cisplatin every 3 weeks for 4 cycles.
Results showed that median disease-free survival – the trial’s primary endpoint—was 28.7 months with gefitinib compared with 18.0 months with chemotherapy (hazard ratio, 0.60; P = .005), Dr. Wu reported in the presscast. Corresponding 3-year disease-free survival rates were 34% and 27%.
The rate of grade 3 or worse adverse events was 12.3% in the gefitinib group, compared with 48.3% in the chemotherapy group. Most types of events were less common with the tyrosine kinase inhibitor, with the exception of rash, diarrhea, and elevation of liver enzymes.
Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Patients in the gefitinib group had a sharply reduced risk of recurrence or death relative to peers in the vinorelbine-cisplatin group (hazard ratio, 0.60; P = .005).
Data source: ADJUVANT, a phase III randomized controlled study of 220 patients with completely resected EGFR-mutant pathological stage II-IIIA (N1-N2) NSCLC.
Disclosures: Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
More early-stage cancer diagnosis since ACA implementation
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: The proportion of cancers that were stage I when diagnosed increased by about 1% after ACA implementation for breast, cervical, lung, and colorectal cancer, while it decreased by 1% for prostate cancer.
Data source: A cohort study of 272,656 patients with these five cancers from the National Cancer Database.
Disclosures: Dr. Han reported that she had no disclosures.
Consider invasive mediastinal staging in higher risk NSCLC patients, despite guidelines
Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) appears to be cost effective for use in non–small cell lung cancer (NSCLC) staging if the prevalence of mediastinal lymph node metastasis (MLNM) is greater than or equal to 2.5%, according to the results of single institution modeling study. In addition, the study found that confirmatory mediastinoscopy should be performed in high-risk patients in cases of negative EBUS-TBNA.
Katarzyna Czarnecka-Kujawa, MD, of the University of Toronto and Toronto General Hospital, and her colleagues performed a decision analysis to compare health outcomes and costs of four mediastinal staging strategies. They assessed the following: no invasive staging, endobronchial ultrasound-guided transbronchial need aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA results were negative. They determined incremental cost-effectiveness ratios (ICER) for all strategies and performed comprehensive sensitivity analyses using a willingness to pay threshold of $80,000 [Canadian]/quality adjusted life-year (QALY).
They used data obtained for staging, outcomes, and costs from the patients in the lung cancer program at the Toronto General Hospital from Jan. 1, 2005 to Dec. 31, 2014, as detailed in a report published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2017. doi: 10.1016/j.jtcvs.2016.12.048).
After exclusions, they utilized a final case count of 499 cases for developing their surgical and procedure cost analysis, and a total of 750 cases in their endoscopy database for endoscopy analysis. For the base-case analysis, they assumed a prevalence of mediastinal metastasis of 9%, and obtained the prevalence of a pathologic lymph nodal stage disease following EBUS-TBNA from their institutional data.
Their results showed that EBUS-TBNA followed by mediastinoscopy was the strategy that resulted in the highest QALYs, but that it had a prohibitive ICER of greater than $1.4 million/QALY. Accordingly, it may not be justifiable to use mediastinoscopy after negative EBUS-TBNA in all patients, the researchers noted. However, the researchers’ data suggest that invasive screening may be justified in a very-low-risk population (MLNM above 2.5%).
In addition, the researchers stated that “[the] benefit conveyed by detecting mediastinal metastatic disease becomes more apparent as the prevalence of MLNM increases, with confirmatory mediastinoscopy becoming cost effective in cases of negative EBUS-TBNA in patients with moderate to high probability of MLNM” (greater than 57%).
Our model points out that there is a well-defined role for the use of different modalities, including mediastinoscopy. This stresses the need for ongoing focus on maintenance of competency and skill acquisition in mediastinoscopy and EBUS-TBNA by currently practicing and future thoracic surgeons respectively,” the researchers concluded.
Dr. Czarnecka-Kujawa disclosed that she is a research consultant with Olympus America. The study was funded in part by agencies of the Austrian government.
The authors make a compelling argument for invasive mediastinal staging in patients with clinical stage I non–small cell lung cancer and acknowledge that this conflicts with current guidelines, according to Biniam Kidane, MD, of the University of Manitoba, Winnipeg, in his invited comments on the study in the Journal of Thoracic and Cardiovascular Surgery (2017 Mar 10. doi: 10.1016/j.jtcvs.2017.02.051).
Their single-payer system is likely to have a different willingness-to-pay threshold, compared with those in other countries, especially the United States, where the EBUS-TBNA strategy without invasive staging is likely to remain the cost-effective choice.
“Cost-economic analyses such as these provide a window into the factors necessary to bridge guidelines from the realm of the abstract to the realm of local reality. When interpreting these findings, clinicians should consider: 1) What EBUS resources are available? (2) What is your local EBUS sensitivity? 3) What is the prevalence of MLNM?” Dr. Kidane concluded, with the caveat that such studies are not infallible and models are based on assumptions and must be treated with care.
Dr. Kidane reported no disclosures with regard to commercial support.
The authors make a compelling argument for invasive mediastinal staging in patients with clinical stage I non–small cell lung cancer and acknowledge that this conflicts with current guidelines, according to Biniam Kidane, MD, of the University of Manitoba, Winnipeg, in his invited comments on the study in the Journal of Thoracic and Cardiovascular Surgery (2017 Mar 10. doi: 10.1016/j.jtcvs.2017.02.051).
Their single-payer system is likely to have a different willingness-to-pay threshold, compared with those in other countries, especially the United States, where the EBUS-TBNA strategy without invasive staging is likely to remain the cost-effective choice.
“Cost-economic analyses such as these provide a window into the factors necessary to bridge guidelines from the realm of the abstract to the realm of local reality. When interpreting these findings, clinicians should consider: 1) What EBUS resources are available? (2) What is your local EBUS sensitivity? 3) What is the prevalence of MLNM?” Dr. Kidane concluded, with the caveat that such studies are not infallible and models are based on assumptions and must be treated with care.
Dr. Kidane reported no disclosures with regard to commercial support.
The authors make a compelling argument for invasive mediastinal staging in patients with clinical stage I non–small cell lung cancer and acknowledge that this conflicts with current guidelines, according to Biniam Kidane, MD, of the University of Manitoba, Winnipeg, in his invited comments on the study in the Journal of Thoracic and Cardiovascular Surgery (2017 Mar 10. doi: 10.1016/j.jtcvs.2017.02.051).
Their single-payer system is likely to have a different willingness-to-pay threshold, compared with those in other countries, especially the United States, where the EBUS-TBNA strategy without invasive staging is likely to remain the cost-effective choice.
“Cost-economic analyses such as these provide a window into the factors necessary to bridge guidelines from the realm of the abstract to the realm of local reality. When interpreting these findings, clinicians should consider: 1) What EBUS resources are available? (2) What is your local EBUS sensitivity? 3) What is the prevalence of MLNM?” Dr. Kidane concluded, with the caveat that such studies are not infallible and models are based on assumptions and must be treated with care.
Dr. Kidane reported no disclosures with regard to commercial support.
Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) appears to be cost effective for use in non–small cell lung cancer (NSCLC) staging if the prevalence of mediastinal lymph node metastasis (MLNM) is greater than or equal to 2.5%, according to the results of single institution modeling study. In addition, the study found that confirmatory mediastinoscopy should be performed in high-risk patients in cases of negative EBUS-TBNA.
Katarzyna Czarnecka-Kujawa, MD, of the University of Toronto and Toronto General Hospital, and her colleagues performed a decision analysis to compare health outcomes and costs of four mediastinal staging strategies. They assessed the following: no invasive staging, endobronchial ultrasound-guided transbronchial need aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA results were negative. They determined incremental cost-effectiveness ratios (ICER) for all strategies and performed comprehensive sensitivity analyses using a willingness to pay threshold of $80,000 [Canadian]/quality adjusted life-year (QALY).
They used data obtained for staging, outcomes, and costs from the patients in the lung cancer program at the Toronto General Hospital from Jan. 1, 2005 to Dec. 31, 2014, as detailed in a report published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2017. doi: 10.1016/j.jtcvs.2016.12.048).
After exclusions, they utilized a final case count of 499 cases for developing their surgical and procedure cost analysis, and a total of 750 cases in their endoscopy database for endoscopy analysis. For the base-case analysis, they assumed a prevalence of mediastinal metastasis of 9%, and obtained the prevalence of a pathologic lymph nodal stage disease following EBUS-TBNA from their institutional data.
Their results showed that EBUS-TBNA followed by mediastinoscopy was the strategy that resulted in the highest QALYs, but that it had a prohibitive ICER of greater than $1.4 million/QALY. Accordingly, it may not be justifiable to use mediastinoscopy after negative EBUS-TBNA in all patients, the researchers noted. However, the researchers’ data suggest that invasive screening may be justified in a very-low-risk population (MLNM above 2.5%).
In addition, the researchers stated that “[the] benefit conveyed by detecting mediastinal metastatic disease becomes more apparent as the prevalence of MLNM increases, with confirmatory mediastinoscopy becoming cost effective in cases of negative EBUS-TBNA in patients with moderate to high probability of MLNM” (greater than 57%).
Our model points out that there is a well-defined role for the use of different modalities, including mediastinoscopy. This stresses the need for ongoing focus on maintenance of competency and skill acquisition in mediastinoscopy and EBUS-TBNA by currently practicing and future thoracic surgeons respectively,” the researchers concluded.
Dr. Czarnecka-Kujawa disclosed that she is a research consultant with Olympus America. The study was funded in part by agencies of the Austrian government.
Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) appears to be cost effective for use in non–small cell lung cancer (NSCLC) staging if the prevalence of mediastinal lymph node metastasis (MLNM) is greater than or equal to 2.5%, according to the results of single institution modeling study. In addition, the study found that confirmatory mediastinoscopy should be performed in high-risk patients in cases of negative EBUS-TBNA.
Katarzyna Czarnecka-Kujawa, MD, of the University of Toronto and Toronto General Hospital, and her colleagues performed a decision analysis to compare health outcomes and costs of four mediastinal staging strategies. They assessed the following: no invasive staging, endobronchial ultrasound-guided transbronchial need aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA results were negative. They determined incremental cost-effectiveness ratios (ICER) for all strategies and performed comprehensive sensitivity analyses using a willingness to pay threshold of $80,000 [Canadian]/quality adjusted life-year (QALY).
They used data obtained for staging, outcomes, and costs from the patients in the lung cancer program at the Toronto General Hospital from Jan. 1, 2005 to Dec. 31, 2014, as detailed in a report published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2017. doi: 10.1016/j.jtcvs.2016.12.048).
After exclusions, they utilized a final case count of 499 cases for developing their surgical and procedure cost analysis, and a total of 750 cases in their endoscopy database for endoscopy analysis. For the base-case analysis, they assumed a prevalence of mediastinal metastasis of 9%, and obtained the prevalence of a pathologic lymph nodal stage disease following EBUS-TBNA from their institutional data.
Their results showed that EBUS-TBNA followed by mediastinoscopy was the strategy that resulted in the highest QALYs, but that it had a prohibitive ICER of greater than $1.4 million/QALY. Accordingly, it may not be justifiable to use mediastinoscopy after negative EBUS-TBNA in all patients, the researchers noted. However, the researchers’ data suggest that invasive screening may be justified in a very-low-risk population (MLNM above 2.5%).
In addition, the researchers stated that “[the] benefit conveyed by detecting mediastinal metastatic disease becomes more apparent as the prevalence of MLNM increases, with confirmatory mediastinoscopy becoming cost effective in cases of negative EBUS-TBNA in patients with moderate to high probability of MLNM” (greater than 57%).
Our model points out that there is a well-defined role for the use of different modalities, including mediastinoscopy. This stresses the need for ongoing focus on maintenance of competency and skill acquisition in mediastinoscopy and EBUS-TBNA by currently practicing and future thoracic surgeons respectively,” the researchers concluded.
Dr. Czarnecka-Kujawa disclosed that she is a research consultant with Olympus America. The study was funded in part by agencies of the Austrian government.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point:
Major finding: Once the pathologic lymph nodal stage reaches 57%, EBUS-TBNA followed by mediastinoscopy is cost effective.
Data source: A model of health care outcomes and costs was developed from data obtained from patients treated over a 10-year period at a single institution.
Disclosures: Dr. Czarnecka-Kujawa disclosed that she is a research consultant with Olympus America. The study was funded in part by agencies of the Austrian government.
Salvage chemo for NSCLC more effective after PD-1/PD-L1 inhibitors
GENEVA – Patients with stage IV non–small cell lung cancer (NSCLC) who have disease progression following treatment with an immune checkpoint inhibitor have a 30% better chance of achieving at least a partial response with salvage chemotherapy compared with patients who had received prior chemotherapy but not immunotherapy, according to Swiss and U.S. investigators.
In a study of 82 patients with advanced NSCLC, 18 of 67 patients (27%) who had progressed on an inhibitor of programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) had a partial response to combination chemotherapy, compared with just 1 of 15 (7%) of patients who had not received a checkpoint inhibitor, reported Sacha Rothschild, MD, PhD, of University Hospital Basel, Switzerland, and colleagues.
“The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference, however, warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity,” the researchers wrote in a scientific poster presented at the European Lung Cancer Conference.
Immune checkpoint inhibitors have been shown to be active in patients with late-stage NSCLC who have experienced disease progression following chemotherapy. To see whether salvage chemotherapy could offer any additional benefit to patients who had disease progression on immunotherapy, the investigators conducted a retrospective case-control study. They reviewed 355 patient records, and identified 82 patients – 46 men and 36 women – who met the study criteria.
Of this group, 67 patients had received a PD-1/PD-L1 checkpoint inhibitor, either nivolumab (Opdivo, 56 patients), pembrolizumab (Keytruda, 7), or atezolizumab (Tecentriq, 4). These patients were designated as cases. The remaining 15 patients, who had received prior chemotherapy or chemoradiotherapy only, were designated as controls.
Of all 82 patients, 63 (77%) had adenocarcinomas, 18 (22%) had squamous cell carcinomas, and 1 (1%) had a large-cell carcinoma.
Cases had a mean of 2.37 chemotherapy regimens prior to salvage chemotherapy, and controls had a mean of 1.93. Drugs used in the salvage regimens were docetaxel in 62% of patients, pemetrexed in 20%, gemcitabine in 12%, and paclitaxel in 6%.
The odds ratio for achieving a partial response was 0.30 (95% confidence interval, 0.18-0.50, P less than .0001).
In a multiple logistic regression model, neither age, sex, number of prior chemotherapy regimens, tumor histology, smoking status, nor type of salvage chemotherapy regimen were significantly associated with the likelihood of achieving a partial response.
In a poster discussion session, Simon Ekman, MD, of Karolinska Institute in Stockholm, Sweden, the invited discussant, said that the data from the study are convincing, and raise the question of what to do next.
“The question is how do we combine immunotherapy with chemotherapy? Should we use the immune therapy first, like in this trial, or vice versa, or should we combine concurrently” he said.
The strategy of chemotherapy first is supported by research showing that neoantigens crucial for the immune response are released during chemotherapy and radiotherapy, enabling immunotherapeutic agents to work better, he said.
The study was internally funded. Dr. Rothschild and Dr. Ekman reported no conflicts relevant to the research.
GENEVA – Patients with stage IV non–small cell lung cancer (NSCLC) who have disease progression following treatment with an immune checkpoint inhibitor have a 30% better chance of achieving at least a partial response with salvage chemotherapy compared with patients who had received prior chemotherapy but not immunotherapy, according to Swiss and U.S. investigators.
In a study of 82 patients with advanced NSCLC, 18 of 67 patients (27%) who had progressed on an inhibitor of programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) had a partial response to combination chemotherapy, compared with just 1 of 15 (7%) of patients who had not received a checkpoint inhibitor, reported Sacha Rothschild, MD, PhD, of University Hospital Basel, Switzerland, and colleagues.
“The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference, however, warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity,” the researchers wrote in a scientific poster presented at the European Lung Cancer Conference.
Immune checkpoint inhibitors have been shown to be active in patients with late-stage NSCLC who have experienced disease progression following chemotherapy. To see whether salvage chemotherapy could offer any additional benefit to patients who had disease progression on immunotherapy, the investigators conducted a retrospective case-control study. They reviewed 355 patient records, and identified 82 patients – 46 men and 36 women – who met the study criteria.
Of this group, 67 patients had received a PD-1/PD-L1 checkpoint inhibitor, either nivolumab (Opdivo, 56 patients), pembrolizumab (Keytruda, 7), or atezolizumab (Tecentriq, 4). These patients were designated as cases. The remaining 15 patients, who had received prior chemotherapy or chemoradiotherapy only, were designated as controls.
Of all 82 patients, 63 (77%) had adenocarcinomas, 18 (22%) had squamous cell carcinomas, and 1 (1%) had a large-cell carcinoma.
Cases had a mean of 2.37 chemotherapy regimens prior to salvage chemotherapy, and controls had a mean of 1.93. Drugs used in the salvage regimens were docetaxel in 62% of patients, pemetrexed in 20%, gemcitabine in 12%, and paclitaxel in 6%.
The odds ratio for achieving a partial response was 0.30 (95% confidence interval, 0.18-0.50, P less than .0001).
In a multiple logistic regression model, neither age, sex, number of prior chemotherapy regimens, tumor histology, smoking status, nor type of salvage chemotherapy regimen were significantly associated with the likelihood of achieving a partial response.
In a poster discussion session, Simon Ekman, MD, of Karolinska Institute in Stockholm, Sweden, the invited discussant, said that the data from the study are convincing, and raise the question of what to do next.
“The question is how do we combine immunotherapy with chemotherapy? Should we use the immune therapy first, like in this trial, or vice versa, or should we combine concurrently” he said.
The strategy of chemotherapy first is supported by research showing that neoantigens crucial for the immune response are released during chemotherapy and radiotherapy, enabling immunotherapeutic agents to work better, he said.
The study was internally funded. Dr. Rothschild and Dr. Ekman reported no conflicts relevant to the research.
GENEVA – Patients with stage IV non–small cell lung cancer (NSCLC) who have disease progression following treatment with an immune checkpoint inhibitor have a 30% better chance of achieving at least a partial response with salvage chemotherapy compared with patients who had received prior chemotherapy but not immunotherapy, according to Swiss and U.S. investigators.
In a study of 82 patients with advanced NSCLC, 18 of 67 patients (27%) who had progressed on an inhibitor of programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) had a partial response to combination chemotherapy, compared with just 1 of 15 (7%) of patients who had not received a checkpoint inhibitor, reported Sacha Rothschild, MD, PhD, of University Hospital Basel, Switzerland, and colleagues.
“The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference, however, warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity,” the researchers wrote in a scientific poster presented at the European Lung Cancer Conference.
Immune checkpoint inhibitors have been shown to be active in patients with late-stage NSCLC who have experienced disease progression following chemotherapy. To see whether salvage chemotherapy could offer any additional benefit to patients who had disease progression on immunotherapy, the investigators conducted a retrospective case-control study. They reviewed 355 patient records, and identified 82 patients – 46 men and 36 women – who met the study criteria.
Of this group, 67 patients had received a PD-1/PD-L1 checkpoint inhibitor, either nivolumab (Opdivo, 56 patients), pembrolizumab (Keytruda, 7), or atezolizumab (Tecentriq, 4). These patients were designated as cases. The remaining 15 patients, who had received prior chemotherapy or chemoradiotherapy only, were designated as controls.
Of all 82 patients, 63 (77%) had adenocarcinomas, 18 (22%) had squamous cell carcinomas, and 1 (1%) had a large-cell carcinoma.
Cases had a mean of 2.37 chemotherapy regimens prior to salvage chemotherapy, and controls had a mean of 1.93. Drugs used in the salvage regimens were docetaxel in 62% of patients, pemetrexed in 20%, gemcitabine in 12%, and paclitaxel in 6%.
The odds ratio for achieving a partial response was 0.30 (95% confidence interval, 0.18-0.50, P less than .0001).
In a multiple logistic regression model, neither age, sex, number of prior chemotherapy regimens, tumor histology, smoking status, nor type of salvage chemotherapy regimen were significantly associated with the likelihood of achieving a partial response.
In a poster discussion session, Simon Ekman, MD, of Karolinska Institute in Stockholm, Sweden, the invited discussant, said that the data from the study are convincing, and raise the question of what to do next.
“The question is how do we combine immunotherapy with chemotherapy? Should we use the immune therapy first, like in this trial, or vice versa, or should we combine concurrently” he said.
The strategy of chemotherapy first is supported by research showing that neoantigens crucial for the immune response are released during chemotherapy and radiotherapy, enabling immunotherapeutic agents to work better, he said.
The study was internally funded. Dr. Rothschild and Dr. Ekman reported no conflicts relevant to the research.
FROM ELCC
Key clinical point: Salvage chemotherapy was more effective among patients who had disease progression following immunotherapy in the second line than among patients who received only chemotherapy.
Major finding: Among patients with disease progression while on a checkpoint inhibitor, 18 of 67 had a partial response to salvage chemotherapy, compared with just 1 of 15 controls.
Data source: Retrospective case-control study of 82 patients with advanced NSCLC.
Disclosures: The study was internally funded. Dr. Rothschild and Dr. Ekman reported no conflicts relevant to the research.
Confronting the open chest – Samuel J. Meltzer and the first AATS annual meeting
In retrospect, the founding of the American Association for Thoracic Surgery (AATS) in 1917 may seem surprisingly optimistic, given the status of cardiothoracic surgery as a discipline at that time. While important strides had been made in dealing with open chest wounds, to the modern eye, the field in the second decade of the 20th century seems more characterized by what was not yet possible rather than by what was.
One of the most critical issues holding back the development of cardiothoracic surgery in this early period was the problem of acute pneumothorax that occurred whenever the chest was opened.
As Willy Meyer (1858-1932), second president of the AATS, described the problem at the first AATS annual meeting in 1917: “What is it that happens when the thorax is opened, let us say [for example] by a stab wound in an intercostal space in an affray on the street? Immediately air rushes into the pleural cavity and this normal atmospheric pressure, being greater than the normal pressure within ... the lung contracts to a very small organ around its hilum. Air fills the space formerly occupied by the lung. This condition, with its immediate clinical pathologic consequences, is called ‘acute pneumothorax.’ It has been the stumbling block for almost a century to the proper development of the surgery of the chest. … Carbonic acid is retained in the blood … The accumulation of CO, with its deleterious effect increases, finally ending in the patient’s death.”
But in the first decade of the 20th century, two major and competing techniques evolved to solve the problem, each one represented by the first and second presidents of the fledgling AATS. For a short period of time a controversy seemed to separate the two men, but their views were expressly reconciled at the first annual meeting of the AATS.
The Meltzer/Auer technique was significantly improved upon by the addition of a carbon dioxide absorption method and the creation of a closed circuit apparatus by Dennis Jackson, MD (1878-1980) in 1915. “This fulfilled the criteria of oxygen supply, carbon dioxide absorption, and ether regulation with a hand bag-breather. With this apparatus, respiration could be maintained with the open thorax,” said pioneering thoracic surgeon Rudolf Nissen, MD, and Roger H.L. Wilson, MD, in their Pages in the History of Chest Surgery (Springfield, IL: Charles C. Thomas, 1960).
However, insufflation was not universally applauded when it was first introduced. It was considered a poor second by many who instead embraced the alternate method of preventing chest collapse – the differential pressure–maintaining Sauerbruch chamber. The Sauerbruch chamber was developed by Ernst Ferdinand Sauerbruch (1875-1951) and first reported in 1904 in his paper, “The pathology of open pneumothorax and the bases of my methods for its elimination.”
As described by Nissen and Wilson, “He transformed the operating room into a kind of extended or enlarged pleural cavity, lowering the atmospheric pressure by vacuum. The head of the patient was outside the operating room, tightly sealed at the neck. This ‘pneumatic chamber’ solved in an ideal way the problem of negative pleural pressure.”
Sauerbruch was aware of the Meltzer/Auer technique, but specifically rejected it, and his powerful influence in Germany helped to prevent it from being adopted there.
Among the earliest and most vocal advocates of using the Sauerbruch negative pressure chamber approach in the United States was Dr. Meyer. Both he and Dr. Meltzer addressed the issue and the controversy at the first meeting of the AATS in 1917.
“You probably remember the little battle between differential pressure and intratracheal insufflation. It occurred only 8 years ago; but it seems now like history. When I presented my paper on intratracheal insufflation at the New York Academy of Medicine, my views were opposed, in the interest of conservatism in surgery, by three able surgeons,” Dr. Meltzer said in his address.
“Now, these same surgeons are among the principal founders of the American Association for Thoracic Surgery, and my being the first presiding officer of the Association is due exclusively to their generous spirit and not to any merits of mine. This is my little story of how the introduction of a stomach tube carried a mere medical man into the presidential chair of a national surgical association.”
Dr. Meyer, one of the three surgeons mentioned by Dr. Meltzer, responded shortly thereafter in his own speech at the meeting: “Dr. Meltzer mentioned in his inaugural address today that, in the discussion following his presentation of the matter before the New York Academy of Medicine his views were opposed, in the interest of conservatism in surgery, by three surgeons.
“Inasmuch as I was one of the three, I would, in explanation, here state that ... at that very time it was reported to me that Dr. Meltzer had stated that in his opinion thoracic operations on human beings could be done in a much simpler way than by working in the negative chamber; that a catheter in the trachea and bellows was all that was needed. He, a physiologist who had always done scientific surgical work on animals, certainly found these paraphernalia sufficient. I personally had meanwhile seen and learned to admire the absolutely reliable working of the mechanism of the chamber, without the possibility of doing the slightest harm to the patient.
“In my remarks on that memorable evening at the New York Academy of Medicine, I therefore tried to impress upon my colleagues the great importance of absolute safety. I stated that no matter what apparatus we might use in thoracic surgery on the usually much run down human being, it must be so constructed that it could not possibly do harm to the patient. I further stated that I would be only too happy to personally use intratracheal insufflation as soon as it was sufficiently perfected to render it safe under all conditions. … I want to lay stress upon the statement that I for my part have never been in opposition, but rather in full accord with his splendid discovery. The fact is that I personally have been among the very first in New York to use intratracheal insufflation in thoracic operations upon the human subject,” said Dr. Meyer.
“But, please bear in mind … that only the use of the differential pressure method – no matter what the apparatus – enables the surgeon to work in the thorax with the same equanimity and tranquility as in the abdomen,” he summarized.
So by the early years of the founding of the AATS, no matter the barriers that remained, the fact that thoracic surgery had reached the same level of confidence in terms of attempting operations as had already existed for the abdomen permitted the fledgling association to move forward with a confidence and optimism that had not existed before, when opening the chest in the operating room was generally considered deadly.
Sources
Meltzer, S. J., 1917. First President’s Address. http://t.aats.org/annualmeeting/Program-Books/50th-Anniversary-Book/First-Presidents-Address.cgi
Meyer, W., 1917. Surgery Within the Past Fourteen Years. http://t.aats.org/annualmeeting/Program-Books/50th-Anniversary-Book/A-Review-of-the-Evolution-of-Thoracic-Surgery-Within-the-Pas.cgi
Nissen, R., Wilson, R.H.L. Pages in the History of Chest Surgery. Springfield, IL: Charles C. Thomas, 1960.
In retrospect, the founding of the American Association for Thoracic Surgery (AATS) in 1917 may seem surprisingly optimistic, given the status of cardiothoracic surgery as a discipline at that time. While important strides had been made in dealing with open chest wounds, to the modern eye, the field in the second decade of the 20th century seems more characterized by what was not yet possible rather than by what was.
One of the most critical issues holding back the development of cardiothoracic surgery in this early period was the problem of acute pneumothorax that occurred whenever the chest was opened.
As Willy Meyer (1858-1932), second president of the AATS, described the problem at the first AATS annual meeting in 1917: “What is it that happens when the thorax is opened, let us say [for example] by a stab wound in an intercostal space in an affray on the street? Immediately air rushes into the pleural cavity and this normal atmospheric pressure, being greater than the normal pressure within ... the lung contracts to a very small organ around its hilum. Air fills the space formerly occupied by the lung. This condition, with its immediate clinical pathologic consequences, is called ‘acute pneumothorax.’ It has been the stumbling block for almost a century to the proper development of the surgery of the chest. … Carbonic acid is retained in the blood … The accumulation of CO, with its deleterious effect increases, finally ending in the patient’s death.”
But in the first decade of the 20th century, two major and competing techniques evolved to solve the problem, each one represented by the first and second presidents of the fledgling AATS. For a short period of time a controversy seemed to separate the two men, but their views were expressly reconciled at the first annual meeting of the AATS.
The Meltzer/Auer technique was significantly improved upon by the addition of a carbon dioxide absorption method and the creation of a closed circuit apparatus by Dennis Jackson, MD (1878-1980) in 1915. “This fulfilled the criteria of oxygen supply, carbon dioxide absorption, and ether regulation with a hand bag-breather. With this apparatus, respiration could be maintained with the open thorax,” said pioneering thoracic surgeon Rudolf Nissen, MD, and Roger H.L. Wilson, MD, in their Pages in the History of Chest Surgery (Springfield, IL: Charles C. Thomas, 1960).
However, insufflation was not universally applauded when it was first introduced. It was considered a poor second by many who instead embraced the alternate method of preventing chest collapse – the differential pressure–maintaining Sauerbruch chamber. The Sauerbruch chamber was developed by Ernst Ferdinand Sauerbruch (1875-1951) and first reported in 1904 in his paper, “The pathology of open pneumothorax and the bases of my methods for its elimination.”
As described by Nissen and Wilson, “He transformed the operating room into a kind of extended or enlarged pleural cavity, lowering the atmospheric pressure by vacuum. The head of the patient was outside the operating room, tightly sealed at the neck. This ‘pneumatic chamber’ solved in an ideal way the problem of negative pleural pressure.”
Sauerbruch was aware of the Meltzer/Auer technique, but specifically rejected it, and his powerful influence in Germany helped to prevent it from being adopted there.
Among the earliest and most vocal advocates of using the Sauerbruch negative pressure chamber approach in the United States was Dr. Meyer. Both he and Dr. Meltzer addressed the issue and the controversy at the first meeting of the AATS in 1917.
“You probably remember the little battle between differential pressure and intratracheal insufflation. It occurred only 8 years ago; but it seems now like history. When I presented my paper on intratracheal insufflation at the New York Academy of Medicine, my views were opposed, in the interest of conservatism in surgery, by three able surgeons,” Dr. Meltzer said in his address.
“Now, these same surgeons are among the principal founders of the American Association for Thoracic Surgery, and my being the first presiding officer of the Association is due exclusively to their generous spirit and not to any merits of mine. This is my little story of how the introduction of a stomach tube carried a mere medical man into the presidential chair of a national surgical association.”
Dr. Meyer, one of the three surgeons mentioned by Dr. Meltzer, responded shortly thereafter in his own speech at the meeting: “Dr. Meltzer mentioned in his inaugural address today that, in the discussion following his presentation of the matter before the New York Academy of Medicine his views were opposed, in the interest of conservatism in surgery, by three surgeons.
“Inasmuch as I was one of the three, I would, in explanation, here state that ... at that very time it was reported to me that Dr. Meltzer had stated that in his opinion thoracic operations on human beings could be done in a much simpler way than by working in the negative chamber; that a catheter in the trachea and bellows was all that was needed. He, a physiologist who had always done scientific surgical work on animals, certainly found these paraphernalia sufficient. I personally had meanwhile seen and learned to admire the absolutely reliable working of the mechanism of the chamber, without the possibility of doing the slightest harm to the patient.
“In my remarks on that memorable evening at the New York Academy of Medicine, I therefore tried to impress upon my colleagues the great importance of absolute safety. I stated that no matter what apparatus we might use in thoracic surgery on the usually much run down human being, it must be so constructed that it could not possibly do harm to the patient. I further stated that I would be only too happy to personally use intratracheal insufflation as soon as it was sufficiently perfected to render it safe under all conditions. … I want to lay stress upon the statement that I for my part have never been in opposition, but rather in full accord with his splendid discovery. The fact is that I personally have been among the very first in New York to use intratracheal insufflation in thoracic operations upon the human subject,” said Dr. Meyer.
“But, please bear in mind … that only the use of the differential pressure method – no matter what the apparatus – enables the surgeon to work in the thorax with the same equanimity and tranquility as in the abdomen,” he summarized.
So by the early years of the founding of the AATS, no matter the barriers that remained, the fact that thoracic surgery had reached the same level of confidence in terms of attempting operations as had already existed for the abdomen permitted the fledgling association to move forward with a confidence and optimism that had not existed before, when opening the chest in the operating room was generally considered deadly.
Sources
Meltzer, S. J., 1917. First President’s Address. http://t.aats.org/annualmeeting/Program-Books/50th-Anniversary-Book/First-Presidents-Address.cgi
Meyer, W., 1917. Surgery Within the Past Fourteen Years. http://t.aats.org/annualmeeting/Program-Books/50th-Anniversary-Book/A-Review-of-the-Evolution-of-Thoracic-Surgery-Within-the-Pas.cgi
Nissen, R., Wilson, R.H.L. Pages in the History of Chest Surgery. Springfield, IL: Charles C. Thomas, 1960.
In retrospect, the founding of the American Association for Thoracic Surgery (AATS) in 1917 may seem surprisingly optimistic, given the status of cardiothoracic surgery as a discipline at that time. While important strides had been made in dealing with open chest wounds, to the modern eye, the field in the second decade of the 20th century seems more characterized by what was not yet possible rather than by what was.
One of the most critical issues holding back the development of cardiothoracic surgery in this early period was the problem of acute pneumothorax that occurred whenever the chest was opened.
As Willy Meyer (1858-1932), second president of the AATS, described the problem at the first AATS annual meeting in 1917: “What is it that happens when the thorax is opened, let us say [for example] by a stab wound in an intercostal space in an affray on the street? Immediately air rushes into the pleural cavity and this normal atmospheric pressure, being greater than the normal pressure within ... the lung contracts to a very small organ around its hilum. Air fills the space formerly occupied by the lung. This condition, with its immediate clinical pathologic consequences, is called ‘acute pneumothorax.’ It has been the stumbling block for almost a century to the proper development of the surgery of the chest. … Carbonic acid is retained in the blood … The accumulation of CO, with its deleterious effect increases, finally ending in the patient’s death.”
But in the first decade of the 20th century, two major and competing techniques evolved to solve the problem, each one represented by the first and second presidents of the fledgling AATS. For a short period of time a controversy seemed to separate the two men, but their views were expressly reconciled at the first annual meeting of the AATS.
The Meltzer/Auer technique was significantly improved upon by the addition of a carbon dioxide absorption method and the creation of a closed circuit apparatus by Dennis Jackson, MD (1878-1980) in 1915. “This fulfilled the criteria of oxygen supply, carbon dioxide absorption, and ether regulation with a hand bag-breather. With this apparatus, respiration could be maintained with the open thorax,” said pioneering thoracic surgeon Rudolf Nissen, MD, and Roger H.L. Wilson, MD, in their Pages in the History of Chest Surgery (Springfield, IL: Charles C. Thomas, 1960).
However, insufflation was not universally applauded when it was first introduced. It was considered a poor second by many who instead embraced the alternate method of preventing chest collapse – the differential pressure–maintaining Sauerbruch chamber. The Sauerbruch chamber was developed by Ernst Ferdinand Sauerbruch (1875-1951) and first reported in 1904 in his paper, “The pathology of open pneumothorax and the bases of my methods for its elimination.”
As described by Nissen and Wilson, “He transformed the operating room into a kind of extended or enlarged pleural cavity, lowering the atmospheric pressure by vacuum. The head of the patient was outside the operating room, tightly sealed at the neck. This ‘pneumatic chamber’ solved in an ideal way the problem of negative pleural pressure.”
Sauerbruch was aware of the Meltzer/Auer technique, but specifically rejected it, and his powerful influence in Germany helped to prevent it from being adopted there.
Among the earliest and most vocal advocates of using the Sauerbruch negative pressure chamber approach in the United States was Dr. Meyer. Both he and Dr. Meltzer addressed the issue and the controversy at the first meeting of the AATS in 1917.
“You probably remember the little battle between differential pressure and intratracheal insufflation. It occurred only 8 years ago; but it seems now like history. When I presented my paper on intratracheal insufflation at the New York Academy of Medicine, my views were opposed, in the interest of conservatism in surgery, by three able surgeons,” Dr. Meltzer said in his address.
“Now, these same surgeons are among the principal founders of the American Association for Thoracic Surgery, and my being the first presiding officer of the Association is due exclusively to their generous spirit and not to any merits of mine. This is my little story of how the introduction of a stomach tube carried a mere medical man into the presidential chair of a national surgical association.”
Dr. Meyer, one of the three surgeons mentioned by Dr. Meltzer, responded shortly thereafter in his own speech at the meeting: “Dr. Meltzer mentioned in his inaugural address today that, in the discussion following his presentation of the matter before the New York Academy of Medicine his views were opposed, in the interest of conservatism in surgery, by three surgeons.
“Inasmuch as I was one of the three, I would, in explanation, here state that ... at that very time it was reported to me that Dr. Meltzer had stated that in his opinion thoracic operations on human beings could be done in a much simpler way than by working in the negative chamber; that a catheter in the trachea and bellows was all that was needed. He, a physiologist who had always done scientific surgical work on animals, certainly found these paraphernalia sufficient. I personally had meanwhile seen and learned to admire the absolutely reliable working of the mechanism of the chamber, without the possibility of doing the slightest harm to the patient.
“In my remarks on that memorable evening at the New York Academy of Medicine, I therefore tried to impress upon my colleagues the great importance of absolute safety. I stated that no matter what apparatus we might use in thoracic surgery on the usually much run down human being, it must be so constructed that it could not possibly do harm to the patient. I further stated that I would be only too happy to personally use intratracheal insufflation as soon as it was sufficiently perfected to render it safe under all conditions. … I want to lay stress upon the statement that I for my part have never been in opposition, but rather in full accord with his splendid discovery. The fact is that I personally have been among the very first in New York to use intratracheal insufflation in thoracic operations upon the human subject,” said Dr. Meyer.
“But, please bear in mind … that only the use of the differential pressure method – no matter what the apparatus – enables the surgeon to work in the thorax with the same equanimity and tranquility as in the abdomen,” he summarized.
So by the early years of the founding of the AATS, no matter the barriers that remained, the fact that thoracic surgery had reached the same level of confidence in terms of attempting operations as had already existed for the abdomen permitted the fledgling association to move forward with a confidence and optimism that had not existed before, when opening the chest in the operating room was generally considered deadly.
Sources
Meltzer, S. J., 1917. First President’s Address. http://t.aats.org/annualmeeting/Program-Books/50th-Anniversary-Book/First-Presidents-Address.cgi
Meyer, W., 1917. Surgery Within the Past Fourteen Years. http://t.aats.org/annualmeeting/Program-Books/50th-Anniversary-Book/A-Review-of-the-Evolution-of-Thoracic-Surgery-Within-the-Pas.cgi
Nissen, R., Wilson, R.H.L. Pages in the History of Chest Surgery. Springfield, IL: Charles C. Thomas, 1960.