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Nivolumab effective in PD-L1–deficient lung cancers
VIENNA – The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.
“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.
A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.
Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.
In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.
CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.
In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.
The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.
Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.
The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.
In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.
The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.
Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.
The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.
In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.
The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.
Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.
VIENNA – The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.
“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.
A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.
Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.
In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.
CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.
“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.
A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.
Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.
In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.
CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: When tumors had at least 1% PD-L1 expression, objective response rates were 31% with nivolumab and 12% with docetaxel.
Data source: CheckMate057, a pivotal trial of nivolumab that enrolled 592 patients with advanced, nonsquamous non–small cell lung cancer.
Disclosures: CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
PD-L1 testing in NSCLC patients shows high concordance
VIENNA – Several different tests for PD-L1 levels in tumor cells of patients with metastatic non–small cell lung cancer showed high concordance when run at seven French centers, boosting confidence in the clinical utility of this testing to guide first-line pembrolizumab treatment of patients with this cancer.
Among 27 laboratory-developed tests for PD-L1 (programmed death–ligand 1) levels in tumor cells that used any one of three prespecified testing platforms (made by Dako, Ventana, or Leica), 14 (52%) had “similar” concordance when compared with reference assays, Julien Adam, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer. “These results will provide the basis for making national recommendations for PD-L1 testing in patients with non–small cell lung cancer [NSCLC]” in France, added Dr. Adam, a pathologist at Gustave Roussy Cancer Center in Paris. “We expect to produce recommendations by the second half of 2017.”
Although the results came entirely from French centers, the results will also likely influence U.S. practice, predicted Shirish M. Gadgeel, MD, a thoracic oncologist at the Karmanos Cancer Institute in Detroit. The approval pembrolizumab (Keytruda) received from the Food and Drug Administration in October specified that patients with metastatic NSCLC had to show PD-L1 expression in the tumor using a FDA-approved test to receive pembrolizumab as first-line treatment.
“Before pembrolizumab’s approval there was no incentive to do PD-L1 testing,” but now it is becoming routine, he said. “It has been challenging to U.S. laboratories to decide which platform and antibody to use. Harmonization gives us confidence that if you have a platform and appropriate antibody you should be able to use the results clinically. I think the French results can be extrapolated” to U.S. practice because the results “came from multiple labs using multiple antibodies and platforms,” Dr. Gadgeel said.
The French study arranged for PD-L1 testing of NSCLC specimens from 41 patients selected as broadly representative of PD-L1 expression levels. The seven participating centers used a Dako (three centers), Ventana (two centers), or Leica (two centers) testing platform and one of five available antibodies that bind PD-L1. Every center ran tests that depended on different antibodies, and tests occurred on both tumor cells and immune cells. In total the seven testing sites collectively performed 35 stainings on each specimen for a total of 1,435 slides. In tumor cells, the overall, weighted kappa coefficient for concordance was 0.81 for tests that used the SP263 antibody and 0.78 for those using the E1L3N antibody, both high enough to make them potential candidates for routine use, said Dr. Adam. The 28-8 and 22C3 antibodies also showed high concordance levels. In contrast, some antibodies used at certain centers produced unacceptable results with concordance coefficients of less than 0.5. The best performing antibody overall was SP263.
No test measuring PD-L1 level in immune cells had an acceptable concordance rate, Dr. Adam also reported.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Researchers have developed several different antibodies for measuring levels of PD-L1 in tumor cells and the antibodies can be used in several different testing platforms. Although most laboratories focus on using one specific immunohistochemical platform, the overall status of real-world PD-L1 testing is messy.
In the results reported by Dr. Adam, concordance weighted kappa coefficients of 0.8 or higher show extremely good concordance, and coefficients of 0.6-0.79 show good concordance. Several of the tests and testing sites reported by Dr. Adam showed concordance coefficients within these ranges. In certain other cases the concordance coefficients were very low, which prompts concern about the reliability of these low-scoring tests. The results show that the results you see in one laboratory with a specific antibody and platform test may not always remain consistent with the same antibody and platform used elsewhere.
Michael Boyer, MD, is a professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from AstraZeneca, Bristol-Myers Squibb, Clovis, Eli Lilly, Pfizer, and Roche. He made these comments as designated discussant for the report.
Researchers have developed several different antibodies for measuring levels of PD-L1 in tumor cells and the antibodies can be used in several different testing platforms. Although most laboratories focus on using one specific immunohistochemical platform, the overall status of real-world PD-L1 testing is messy.
In the results reported by Dr. Adam, concordance weighted kappa coefficients of 0.8 or higher show extremely good concordance, and coefficients of 0.6-0.79 show good concordance. Several of the tests and testing sites reported by Dr. Adam showed concordance coefficients within these ranges. In certain other cases the concordance coefficients were very low, which prompts concern about the reliability of these low-scoring tests. The results show that the results you see in one laboratory with a specific antibody and platform test may not always remain consistent with the same antibody and platform used elsewhere.
Michael Boyer, MD, is a professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from AstraZeneca, Bristol-Myers Squibb, Clovis, Eli Lilly, Pfizer, and Roche. He made these comments as designated discussant for the report.
Researchers have developed several different antibodies for measuring levels of PD-L1 in tumor cells and the antibodies can be used in several different testing platforms. Although most laboratories focus on using one specific immunohistochemical platform, the overall status of real-world PD-L1 testing is messy.
In the results reported by Dr. Adam, concordance weighted kappa coefficients of 0.8 or higher show extremely good concordance, and coefficients of 0.6-0.79 show good concordance. Several of the tests and testing sites reported by Dr. Adam showed concordance coefficients within these ranges. In certain other cases the concordance coefficients were very low, which prompts concern about the reliability of these low-scoring tests. The results show that the results you see in one laboratory with a specific antibody and platform test may not always remain consistent with the same antibody and platform used elsewhere.
Michael Boyer, MD, is a professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from AstraZeneca, Bristol-Myers Squibb, Clovis, Eli Lilly, Pfizer, and Roche. He made these comments as designated discussant for the report.
VIENNA – Several different tests for PD-L1 levels in tumor cells of patients with metastatic non–small cell lung cancer showed high concordance when run at seven French centers, boosting confidence in the clinical utility of this testing to guide first-line pembrolizumab treatment of patients with this cancer.
Among 27 laboratory-developed tests for PD-L1 (programmed death–ligand 1) levels in tumor cells that used any one of three prespecified testing platforms (made by Dako, Ventana, or Leica), 14 (52%) had “similar” concordance when compared with reference assays, Julien Adam, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer. “These results will provide the basis for making national recommendations for PD-L1 testing in patients with non–small cell lung cancer [NSCLC]” in France, added Dr. Adam, a pathologist at Gustave Roussy Cancer Center in Paris. “We expect to produce recommendations by the second half of 2017.”
Although the results came entirely from French centers, the results will also likely influence U.S. practice, predicted Shirish M. Gadgeel, MD, a thoracic oncologist at the Karmanos Cancer Institute in Detroit. The approval pembrolizumab (Keytruda) received from the Food and Drug Administration in October specified that patients with metastatic NSCLC had to show PD-L1 expression in the tumor using a FDA-approved test to receive pembrolizumab as first-line treatment.
“Before pembrolizumab’s approval there was no incentive to do PD-L1 testing,” but now it is becoming routine, he said. “It has been challenging to U.S. laboratories to decide which platform and antibody to use. Harmonization gives us confidence that if you have a platform and appropriate antibody you should be able to use the results clinically. I think the French results can be extrapolated” to U.S. practice because the results “came from multiple labs using multiple antibodies and platforms,” Dr. Gadgeel said.
The French study arranged for PD-L1 testing of NSCLC specimens from 41 patients selected as broadly representative of PD-L1 expression levels. The seven participating centers used a Dako (three centers), Ventana (two centers), or Leica (two centers) testing platform and one of five available antibodies that bind PD-L1. Every center ran tests that depended on different antibodies, and tests occurred on both tumor cells and immune cells. In total the seven testing sites collectively performed 35 stainings on each specimen for a total of 1,435 slides. In tumor cells, the overall, weighted kappa coefficient for concordance was 0.81 for tests that used the SP263 antibody and 0.78 for those using the E1L3N antibody, both high enough to make them potential candidates for routine use, said Dr. Adam. The 28-8 and 22C3 antibodies also showed high concordance levels. In contrast, some antibodies used at certain centers produced unacceptable results with concordance coefficients of less than 0.5. The best performing antibody overall was SP263.
No test measuring PD-L1 level in immune cells had an acceptable concordance rate, Dr. Adam also reported.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Several different tests for PD-L1 levels in tumor cells of patients with metastatic non–small cell lung cancer showed high concordance when run at seven French centers, boosting confidence in the clinical utility of this testing to guide first-line pembrolizumab treatment of patients with this cancer.
Among 27 laboratory-developed tests for PD-L1 (programmed death–ligand 1) levels in tumor cells that used any one of three prespecified testing platforms (made by Dako, Ventana, or Leica), 14 (52%) had “similar” concordance when compared with reference assays, Julien Adam, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer. “These results will provide the basis for making national recommendations for PD-L1 testing in patients with non–small cell lung cancer [NSCLC]” in France, added Dr. Adam, a pathologist at Gustave Roussy Cancer Center in Paris. “We expect to produce recommendations by the second half of 2017.”
Although the results came entirely from French centers, the results will also likely influence U.S. practice, predicted Shirish M. Gadgeel, MD, a thoracic oncologist at the Karmanos Cancer Institute in Detroit. The approval pembrolizumab (Keytruda) received from the Food and Drug Administration in October specified that patients with metastatic NSCLC had to show PD-L1 expression in the tumor using a FDA-approved test to receive pembrolizumab as first-line treatment.
“Before pembrolizumab’s approval there was no incentive to do PD-L1 testing,” but now it is becoming routine, he said. “It has been challenging to U.S. laboratories to decide which platform and antibody to use. Harmonization gives us confidence that if you have a platform and appropriate antibody you should be able to use the results clinically. I think the French results can be extrapolated” to U.S. practice because the results “came from multiple labs using multiple antibodies and platforms,” Dr. Gadgeel said.
The French study arranged for PD-L1 testing of NSCLC specimens from 41 patients selected as broadly representative of PD-L1 expression levels. The seven participating centers used a Dako (three centers), Ventana (two centers), or Leica (two centers) testing platform and one of five available antibodies that bind PD-L1. Every center ran tests that depended on different antibodies, and tests occurred on both tumor cells and immune cells. In total the seven testing sites collectively performed 35 stainings on each specimen for a total of 1,435 slides. In tumor cells, the overall, weighted kappa coefficient for concordance was 0.81 for tests that used the SP263 antibody and 0.78 for those using the E1L3N antibody, both high enough to make them potential candidates for routine use, said Dr. Adam. The 28-8 and 22C3 antibodies also showed high concordance levels. In contrast, some antibodies used at certain centers produced unacceptable results with concordance coefficients of less than 0.5. The best performing antibody overall was SP263.
No test measuring PD-L1 level in immune cells had an acceptable concordance rate, Dr. Adam also reported.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: The concordance weighted kappa coefficient was highest for tests using the SP263 antibody, with an average coefficient of 0.81.
Data source: Forty-one non–small cell lung cancer specimens subjected to a total of 35 different tests.
Disclosures: Funding for the study came from AstraZeneca, Bristol Myers Squibb, Merck Sharp and Dohme, and Roche. Dr. Adam has been a consultant to AstraZeneca, Bristol-Myers Squibb, HalioDx, Merck Sharp and Dohme, and Roche. Dr. Gadgeel has been a speaker on behalf of Eli Lilly, Genentech, and GlaxoSmithKline and has received research funding from AstraZeneca, Eli Lilly, and Genentech. Dr. Brahmer has served on an advisory board for Merck.
VIDEO: Improved QOL an added benefit of pembrolizumab for NSCLC patients
VIENNA – Patients with metastatic non–small-cell lung cancer with high levels of PD-L1 who received first-line pembrolizumab treatment had clinically meaningful improvement in their quality of life, compared with patients randomized to chemotherapy, in a prespecified secondary analysis of data from the drug’s pivotal trial.
This boost in quality of life as well as other measures of health status add to the pivotal trial’s primary finding of significantly increased progression-free survival compared with chemotherapy, as well as previously-reported secondary findings of superior overall survival, objective response rate, and safety with pembrolizumab compared with chemotherapy (N Engl J Med. 2016 Nov 10;375[19]:1823-33), Julie R. Brahmer, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The primary endpoint of the Study of Pembrolizumab Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non–Small Cell Lung Cancer (KEYNOTE-024) showed an average 4.3-month increase in progression-free survival with pembrolizumab immunotherapy, compared with a standard chemotherapy regimen.
Improved quality of life on top of improved efficacy and safety is an important added benefit from pembrolizumab that should further spur its widespread adoption as first-line treatment for approved patients, Dr. Brahmer said in a video interview.
“When you talk about improving efficacy by months, patients and physicians want to also see improved quality of life,” said Dr. Brahmer, director of thoracic oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore. “If symptoms are not improved or there are a ton of side effects with the treatment then use might be low.”
Based on its performance in KEYNOTE-024, pembrolizumab (Keytruda) received Food and Drug Administration approval on Oct. 24, 2016, as first-line treatment for patients with metastatic non–small-cell lung cancer that has a tumor proportion score of at least 50% for programmed death ligand 1 (PD-L1). Pembrolizumab is a monoclonal antibody that binds and blocks PD-1, the immune-cell receptor that tumor-cell PD-L1 binds to make immune cells less active. Other new immune checkpoint inhibitor drugs that act by blocking PD-1 or PD-L1 have shown similar quality of life benefits, she noted.
Routine availability of pembrolizumab as initial treatment for patients who have tumors with this level of PD-L1 expression (and also have no EGFR or ALK genomic aberrations) is shifting practice, Dr. Brahmer said.
“It’s catching on. The limitation right now is making sure patients get tested” for their PD-L1 tumor proportion score at the time they are first diagnosed. “Medical oncologists need to educate pathologists that we need this testing automatically, upfront. It’s not there yet,” she said.
Patients also are enthused. “There is a lot of chemo-exhaustion among patients. They are looking for something different, and something that uses their immune system makes sense.” But only about one quarter of patients have tumors with this level of PD-L1 expression; the others must start chemotherapy first before trying immunotherapy, unless they have an EGFR mutation. Out-of-pocket cost for pembrolizumab is also a major issues for many patients, she said.
KEYNOTE-024 randomized 305 patients at 102 international sites and followed patients for a median of 11 months. Dr. Brahmer and her associates made two primary analyses of patient-reported outcomes. One was measurement of global health status at 15 weeks after the start of treatment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire designed to assess quality of life. Weighted averaging of the EORTC QCQ-C30 scores showed a mean improvement of 7.8 points (P = .002) in the pembrolizumab patients compared with the chemotherapy patients, a difference Dr. Brahmer called “clinically meaningful” as well as statistically significant.
A second analysis of patient-reported outcomes used a second EORTC instrument, the QLC-LC13, which combines assessment of cough, chest pain, and dyspnea. Treatment with pembrolizumab significantly reduced the time to deterioration as measured by this questionnaire by a relative 34%, (P = .029).
A third analysis looked at 15 individual function or symptom domains that make up the QLQ-C30. In general, these showed more improvements with pembrolizumab than with chemotherapy. One notable subcategory was fatigue, which showed significant improvement with pembrolizumab compared with a small worsening with chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This is a very nice analysis using a well-validated group of instruments to assess quality of life. The researchers also achieved a high level of compliance, with 79%-85% of patients completing the quality-of life questionnaire at 15 weeks, when the primary measure of health status occurred.
The mean difference of the weighted global health status score of 7.8 points between the pembrolizumab and chemotherapy patients was a little less than a minimally important difference, but in the context of a randomized, controlled trial this difference probably tells us that there is health status improvement in the pembrolizumab patients. In addition, the individual symptom and function domains showed that in general pembrolizumab performed better than chemotherapy.
Michael Boyer, MD , is professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from Pfizer, Roche, Eli Lilly, BMS, AstraZeneca, and Clovis. He made these comments as designated discussant for the report.
This is a very nice analysis using a well-validated group of instruments to assess quality of life. The researchers also achieved a high level of compliance, with 79%-85% of patients completing the quality-of life questionnaire at 15 weeks, when the primary measure of health status occurred.
The mean difference of the weighted global health status score of 7.8 points between the pembrolizumab and chemotherapy patients was a little less than a minimally important difference, but in the context of a randomized, controlled trial this difference probably tells us that there is health status improvement in the pembrolizumab patients. In addition, the individual symptom and function domains showed that in general pembrolizumab performed better than chemotherapy.
Michael Boyer, MD , is professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from Pfizer, Roche, Eli Lilly, BMS, AstraZeneca, and Clovis. He made these comments as designated discussant for the report.
This is a very nice analysis using a well-validated group of instruments to assess quality of life. The researchers also achieved a high level of compliance, with 79%-85% of patients completing the quality-of life questionnaire at 15 weeks, when the primary measure of health status occurred.
The mean difference of the weighted global health status score of 7.8 points between the pembrolizumab and chemotherapy patients was a little less than a minimally important difference, but in the context of a randomized, controlled trial this difference probably tells us that there is health status improvement in the pembrolizumab patients. In addition, the individual symptom and function domains showed that in general pembrolizumab performed better than chemotherapy.
Michael Boyer, MD , is professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from Pfizer, Roche, Eli Lilly, BMS, AstraZeneca, and Clovis. He made these comments as designated discussant for the report.
VIENNA – Patients with metastatic non–small-cell lung cancer with high levels of PD-L1 who received first-line pembrolizumab treatment had clinically meaningful improvement in their quality of life, compared with patients randomized to chemotherapy, in a prespecified secondary analysis of data from the drug’s pivotal trial.
This boost in quality of life as well as other measures of health status add to the pivotal trial’s primary finding of significantly increased progression-free survival compared with chemotherapy, as well as previously-reported secondary findings of superior overall survival, objective response rate, and safety with pembrolizumab compared with chemotherapy (N Engl J Med. 2016 Nov 10;375[19]:1823-33), Julie R. Brahmer, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The primary endpoint of the Study of Pembrolizumab Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non–Small Cell Lung Cancer (KEYNOTE-024) showed an average 4.3-month increase in progression-free survival with pembrolizumab immunotherapy, compared with a standard chemotherapy regimen.
Improved quality of life on top of improved efficacy and safety is an important added benefit from pembrolizumab that should further spur its widespread adoption as first-line treatment for approved patients, Dr. Brahmer said in a video interview.
“When you talk about improving efficacy by months, patients and physicians want to also see improved quality of life,” said Dr. Brahmer, director of thoracic oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore. “If symptoms are not improved or there are a ton of side effects with the treatment then use might be low.”
Based on its performance in KEYNOTE-024, pembrolizumab (Keytruda) received Food and Drug Administration approval on Oct. 24, 2016, as first-line treatment for patients with metastatic non–small-cell lung cancer that has a tumor proportion score of at least 50% for programmed death ligand 1 (PD-L1). Pembrolizumab is a monoclonal antibody that binds and blocks PD-1, the immune-cell receptor that tumor-cell PD-L1 binds to make immune cells less active. Other new immune checkpoint inhibitor drugs that act by blocking PD-1 or PD-L1 have shown similar quality of life benefits, she noted.
Routine availability of pembrolizumab as initial treatment for patients who have tumors with this level of PD-L1 expression (and also have no EGFR or ALK genomic aberrations) is shifting practice, Dr. Brahmer said.
“It’s catching on. The limitation right now is making sure patients get tested” for their PD-L1 tumor proportion score at the time they are first diagnosed. “Medical oncologists need to educate pathologists that we need this testing automatically, upfront. It’s not there yet,” she said.
Patients also are enthused. “There is a lot of chemo-exhaustion among patients. They are looking for something different, and something that uses their immune system makes sense.” But only about one quarter of patients have tumors with this level of PD-L1 expression; the others must start chemotherapy first before trying immunotherapy, unless they have an EGFR mutation. Out-of-pocket cost for pembrolizumab is also a major issues for many patients, she said.
KEYNOTE-024 randomized 305 patients at 102 international sites and followed patients for a median of 11 months. Dr. Brahmer and her associates made two primary analyses of patient-reported outcomes. One was measurement of global health status at 15 weeks after the start of treatment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire designed to assess quality of life. Weighted averaging of the EORTC QCQ-C30 scores showed a mean improvement of 7.8 points (P = .002) in the pembrolizumab patients compared with the chemotherapy patients, a difference Dr. Brahmer called “clinically meaningful” as well as statistically significant.
A second analysis of patient-reported outcomes used a second EORTC instrument, the QLC-LC13, which combines assessment of cough, chest pain, and dyspnea. Treatment with pembrolizumab significantly reduced the time to deterioration as measured by this questionnaire by a relative 34%, (P = .029).
A third analysis looked at 15 individual function or symptom domains that make up the QLQ-C30. In general, these showed more improvements with pembrolizumab than with chemotherapy. One notable subcategory was fatigue, which showed significant improvement with pembrolizumab compared with a small worsening with chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Patients with metastatic non–small-cell lung cancer with high levels of PD-L1 who received first-line pembrolizumab treatment had clinically meaningful improvement in their quality of life, compared with patients randomized to chemotherapy, in a prespecified secondary analysis of data from the drug’s pivotal trial.
This boost in quality of life as well as other measures of health status add to the pivotal trial’s primary finding of significantly increased progression-free survival compared with chemotherapy, as well as previously-reported secondary findings of superior overall survival, objective response rate, and safety with pembrolizumab compared with chemotherapy (N Engl J Med. 2016 Nov 10;375[19]:1823-33), Julie R. Brahmer, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The primary endpoint of the Study of Pembrolizumab Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non–Small Cell Lung Cancer (KEYNOTE-024) showed an average 4.3-month increase in progression-free survival with pembrolizumab immunotherapy, compared with a standard chemotherapy regimen.
Improved quality of life on top of improved efficacy and safety is an important added benefit from pembrolizumab that should further spur its widespread adoption as first-line treatment for approved patients, Dr. Brahmer said in a video interview.
“When you talk about improving efficacy by months, patients and physicians want to also see improved quality of life,” said Dr. Brahmer, director of thoracic oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore. “If symptoms are not improved or there are a ton of side effects with the treatment then use might be low.”
Based on its performance in KEYNOTE-024, pembrolizumab (Keytruda) received Food and Drug Administration approval on Oct. 24, 2016, as first-line treatment for patients with metastatic non–small-cell lung cancer that has a tumor proportion score of at least 50% for programmed death ligand 1 (PD-L1). Pembrolizumab is a monoclonal antibody that binds and blocks PD-1, the immune-cell receptor that tumor-cell PD-L1 binds to make immune cells less active. Other new immune checkpoint inhibitor drugs that act by blocking PD-1 or PD-L1 have shown similar quality of life benefits, she noted.
Routine availability of pembrolizumab as initial treatment for patients who have tumors with this level of PD-L1 expression (and also have no EGFR or ALK genomic aberrations) is shifting practice, Dr. Brahmer said.
“It’s catching on. The limitation right now is making sure patients get tested” for their PD-L1 tumor proportion score at the time they are first diagnosed. “Medical oncologists need to educate pathologists that we need this testing automatically, upfront. It’s not there yet,” she said.
Patients also are enthused. “There is a lot of chemo-exhaustion among patients. They are looking for something different, and something that uses their immune system makes sense.” But only about one quarter of patients have tumors with this level of PD-L1 expression; the others must start chemotherapy first before trying immunotherapy, unless they have an EGFR mutation. Out-of-pocket cost for pembrolizumab is also a major issues for many patients, she said.
KEYNOTE-024 randomized 305 patients at 102 international sites and followed patients for a median of 11 months. Dr. Brahmer and her associates made two primary analyses of patient-reported outcomes. One was measurement of global health status at 15 weeks after the start of treatment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire designed to assess quality of life. Weighted averaging of the EORTC QCQ-C30 scores showed a mean improvement of 7.8 points (P = .002) in the pembrolizumab patients compared with the chemotherapy patients, a difference Dr. Brahmer called “clinically meaningful” as well as statistically significant.
A second analysis of patient-reported outcomes used a second EORTC instrument, the QLC-LC13, which combines assessment of cough, chest pain, and dyspnea. Treatment with pembrolizumab significantly reduced the time to deterioration as measured by this questionnaire by a relative 34%, (P = .029).
A third analysis looked at 15 individual function or symptom domains that make up the QLQ-C30. In general, these showed more improvements with pembrolizumab than with chemotherapy. One notable subcategory was fatigue, which showed significant improvement with pembrolizumab compared with a small worsening with chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: The weighted average change from baseline in QLQ-C30 was 7.8 points higher in pembrolizumab patients compared with chemotherapy patients.
Data source: KEYNOTE-024, a multicenter, international randomized trial comprising 305 patients.
Disclosures: Merck, which markets pembrolizumab (Keytruda), sponsored KEYNOTE-024. Dr. Brahmer has served on an advisory board for Merck.
Toxicity high for SBRT in centrally-located lung tumors
VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.
“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).
“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.
“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.
A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.
Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.
The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.
After a follow-up of 18.6 months, 31 (42%) patients had died.
The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).
Bleeding often occurred without warning and had an acute onset and toll.
Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.
SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.
Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.
“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?
“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”
The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.
“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).
“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.
“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.
A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.
Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.
The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.
After a follow-up of 18.6 months, 31 (42%) patients had died.
The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).
Bleeding often occurred without warning and had an acute onset and toll.
Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.
SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.
Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.
“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?
“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”
The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.
“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).
“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.
“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.
A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.
Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.
The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.
After a follow-up of 18.6 months, 31 (42%) patients had died.
The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).
Bleeding often occurred without warning and had an acute onset and toll.
Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.
SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.
Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.
“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?
“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”
The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
AT WCLC 2016
Key clinical point: Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
Major finding: There was a high rate of grade 3, 4, and 5 toxicities, including six cases of grade 5 bleeding.
Data source: The phase II non-randomized HILUS trial of 74 patients with centrally-located lung tumors treated with SBRT.
Disclosures: The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
c-Myc could be key to alisertib potential in small-cell lung cancer
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
AT WCLC 2016
Key clinical point: Alisertib/paclitaxel is an investigational combination that was tested for the treatment of relapsed or refractory small-cell lung cancer (SCLC).
Major finding: Improved progression-free survival was seen with the combination versus paclitaxel alone (3.2 vs. 2.17 months, P less than .038).
Data source: Randomized, double-blind, multicenter, phase II study of alisertib/paclitaxel versus placebo/paclitaxel in 178 patients with relapsed or refractory SCLC.
Disclosures: The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen had no conflicts of interest to disclose.
Durvalumab could offer option for difficult-to-treat NSCLC
VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.
The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).
Yet the results of ATLANTIC show not only that durvalumab is active, but also that it can produce long-lasting responses in patients who have been treated with a mean of three prior regimens, she reported.
The median duration of response to date was not reached in patients with PD-L1 expression of 25% or less, was 12.3 months in patients with greater than 25% PD-L1 expression, and had again not yet been reached in those with greater than 90% PD-L1 expression. At the time the data were pulled for analysis, June 2016, 18 of 21 patients in the latter group were progression free.
The disease control rate at 6 months was 20.4%, 28.8%, 38.2% for patients with PD-L1 expression of less than 25%, 25%-90%, and greater than 90%, respectively.
“One-year overall survival was about 48% in patients with PD-L1 greater than 25% and about 51% in those with PD-L1 greater than 90%,” Dr. Garassino said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
The respective median OS times for patients with 25% and greater and less than 25% PD-L1 expression were 10.9 (95% CI 8.6-13.6) and 9.3 (95% CI 5.9-10.8) months, and not yet reached for patients with 90% or greater PD-L1 expression.
“Most adverse events were low grade and immune mediated adverse events were easily manageable,” Dr. Garassino said. Overall, 10.2% of patients had grade 3 or 4 treatment-related adverse events and 2.7% had treatment-related adverse events that led to discontinuation.
Any immune-mediated adverse event occurred in 12.3% of patients, of which 6.3% were due to an underactive and 2.4% to a hyperactive thyroid.
“Results are consistent with other anti-PD-1/PD-L1 compounds in metastatic, relapsed NSCLC and we are awaiting the final results of phase III trials to clarify the role of durvalumab [treatment] alone or in combination in NSCLC,” Dr. Garassino said.
Overall, 1,990 patients were screened for inclusion in the ATLANTIC study, which recruited 444 patients with stage IIIB-IV NSCLC who had received at least two prior systemic treatments, one of which had to be platinum based and had a recent (within 3 months) tumor biopsy and archived tissue available for PD-L1 assessment. Dr. Garassino reported results for two of the three cohorts.
Durvalumab was given at an intravenous dose of 10 mg/kg every 2 weeks for up to 1 year. The mean number of prior regimens was 3.2 for patients with less than 25% and greater than or equal to 25% PD-L1 expression combined and 2.6 for those with greater than 90% PD-L1 expression.
“This drug clearly does have activity and we can see that in the response rates, which range from 7% all the way up to 31%,” said Michael Boyer, MBBS, chief clinical officer of Chris O’Brien Lifehouse in Melbourne, who was the invited discussant for the trial. “The higher the PD-L1 expression, the higher the response rate,” he observed.
“There was quite impressive survival, if you bear in mind that this is a third-line, or more than third-line cohort of patients, with a median overall survival in the strongest PD-L1 expressing patients that is clearly going to exceed 1 year” he added.
The big question for the future is what will be the relevance of having an immunotherapy that works well in such a heavily pretreated population when these drugs are more likely to be used second- or even first-line, especially in those who have high PD-L1 expression where the drug seems to be at its most effective, Dr. Boyer said.
AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.
The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).
Yet the results of ATLANTIC show not only that durvalumab is active, but also that it can produce long-lasting responses in patients who have been treated with a mean of three prior regimens, she reported.
The median duration of response to date was not reached in patients with PD-L1 expression of 25% or less, was 12.3 months in patients with greater than 25% PD-L1 expression, and had again not yet been reached in those with greater than 90% PD-L1 expression. At the time the data were pulled for analysis, June 2016, 18 of 21 patients in the latter group were progression free.
The disease control rate at 6 months was 20.4%, 28.8%, 38.2% for patients with PD-L1 expression of less than 25%, 25%-90%, and greater than 90%, respectively.
“One-year overall survival was about 48% in patients with PD-L1 greater than 25% and about 51% in those with PD-L1 greater than 90%,” Dr. Garassino said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
The respective median OS times for patients with 25% and greater and less than 25% PD-L1 expression were 10.9 (95% CI 8.6-13.6) and 9.3 (95% CI 5.9-10.8) months, and not yet reached for patients with 90% or greater PD-L1 expression.
“Most adverse events were low grade and immune mediated adverse events were easily manageable,” Dr. Garassino said. Overall, 10.2% of patients had grade 3 or 4 treatment-related adverse events and 2.7% had treatment-related adverse events that led to discontinuation.
Any immune-mediated adverse event occurred in 12.3% of patients, of which 6.3% were due to an underactive and 2.4% to a hyperactive thyroid.
“Results are consistent with other anti-PD-1/PD-L1 compounds in metastatic, relapsed NSCLC and we are awaiting the final results of phase III trials to clarify the role of durvalumab [treatment] alone or in combination in NSCLC,” Dr. Garassino said.
Overall, 1,990 patients were screened for inclusion in the ATLANTIC study, which recruited 444 patients with stage IIIB-IV NSCLC who had received at least two prior systemic treatments, one of which had to be platinum based and had a recent (within 3 months) tumor biopsy and archived tissue available for PD-L1 assessment. Dr. Garassino reported results for two of the three cohorts.
Durvalumab was given at an intravenous dose of 10 mg/kg every 2 weeks for up to 1 year. The mean number of prior regimens was 3.2 for patients with less than 25% and greater than or equal to 25% PD-L1 expression combined and 2.6 for those with greater than 90% PD-L1 expression.
“This drug clearly does have activity and we can see that in the response rates, which range from 7% all the way up to 31%,” said Michael Boyer, MBBS, chief clinical officer of Chris O’Brien Lifehouse in Melbourne, who was the invited discussant for the trial. “The higher the PD-L1 expression, the higher the response rate,” he observed.
“There was quite impressive survival, if you bear in mind that this is a third-line, or more than third-line cohort of patients, with a median overall survival in the strongest PD-L1 expressing patients that is clearly going to exceed 1 year” he added.
The big question for the future is what will be the relevance of having an immunotherapy that works well in such a heavily pretreated population when these drugs are more likely to be used second- or even first-line, especially in those who have high PD-L1 expression where the drug seems to be at its most effective, Dr. Boyer said.
AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.
The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).
Yet the results of ATLANTIC show not only that durvalumab is active, but also that it can produce long-lasting responses in patients who have been treated with a mean of three prior regimens, she reported.
The median duration of response to date was not reached in patients with PD-L1 expression of 25% or less, was 12.3 months in patients with greater than 25% PD-L1 expression, and had again not yet been reached in those with greater than 90% PD-L1 expression. At the time the data were pulled for analysis, June 2016, 18 of 21 patients in the latter group were progression free.
The disease control rate at 6 months was 20.4%, 28.8%, 38.2% for patients with PD-L1 expression of less than 25%, 25%-90%, and greater than 90%, respectively.
“One-year overall survival was about 48% in patients with PD-L1 greater than 25% and about 51% in those with PD-L1 greater than 90%,” Dr. Garassino said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
The respective median OS times for patients with 25% and greater and less than 25% PD-L1 expression were 10.9 (95% CI 8.6-13.6) and 9.3 (95% CI 5.9-10.8) months, and not yet reached for patients with 90% or greater PD-L1 expression.
“Most adverse events were low grade and immune mediated adverse events were easily manageable,” Dr. Garassino said. Overall, 10.2% of patients had grade 3 or 4 treatment-related adverse events and 2.7% had treatment-related adverse events that led to discontinuation.
Any immune-mediated adverse event occurred in 12.3% of patients, of which 6.3% were due to an underactive and 2.4% to a hyperactive thyroid.
“Results are consistent with other anti-PD-1/PD-L1 compounds in metastatic, relapsed NSCLC and we are awaiting the final results of phase III trials to clarify the role of durvalumab [treatment] alone or in combination in NSCLC,” Dr. Garassino said.
Overall, 1,990 patients were screened for inclusion in the ATLANTIC study, which recruited 444 patients with stage IIIB-IV NSCLC who had received at least two prior systemic treatments, one of which had to be platinum based and had a recent (within 3 months) tumor biopsy and archived tissue available for PD-L1 assessment. Dr. Garassino reported results for two of the three cohorts.
Durvalumab was given at an intravenous dose of 10 mg/kg every 2 weeks for up to 1 year. The mean number of prior regimens was 3.2 for patients with less than 25% and greater than or equal to 25% PD-L1 expression combined and 2.6 for those with greater than 90% PD-L1 expression.
“This drug clearly does have activity and we can see that in the response rates, which range from 7% all the way up to 31%,” said Michael Boyer, MBBS, chief clinical officer of Chris O’Brien Lifehouse in Melbourne, who was the invited discussant for the trial. “The higher the PD-L1 expression, the higher the response rate,” he observed.
“There was quite impressive survival, if you bear in mind that this is a third-line, or more than third-line cohort of patients, with a median overall survival in the strongest PD-L1 expressing patients that is clearly going to exceed 1 year” he added.
The big question for the future is what will be the relevance of having an immunotherapy that works well in such a heavily pretreated population when these drugs are more likely to be used second- or even first-line, especially in those who have high PD-L1 expression where the drug seems to be at its most effective, Dr. Boyer said.
AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
Key clinical point: Durvalumab had substantial antitumor activity and produced long-lasting responses in patients with previously treated advanced non–small-cell lung cancer (NSCLC).
Major finding: Objective response rates of 16.4% and 30.1% were achieved in patients with the highest PD-L1 expression profiles.
Data source: Phase II, open-label, single-arm ATLANTIC trial of 444 patients with relapsed, locally advanced or metastatic NSCLC treated with two or more prior systemic regimens.
Disclosures: AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
Pembrolizumab proves promising for treating advanced SCLC
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
AT WCLC 2016
Key clinical point: Pembrolizumab has antitumor activity in patients with advanced small-cell lung cancer.
Major finding: The objective response rate was 33.3% (95% CI 15.6-55.3%), including one complete and seven partial responses.
Data source: Phase Ib, nonrandomized, multicohort trial of 24 heavily pretreated patients with extensive-disease small-cell lung cancer.
Disclosures: Merck funded the study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIDEO: Pivotal results nail osimertinib’s role in NSCLC
VIENNA – Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that received U.S. marketing approval in November 2015 as second-line treatment for selected patients with non–small-cell lung cancer based on phase II trial data, now has the pivotal-trial results that completely justify that action.
During a median follow-up of just over 8 months, patients who had progressed on their first-line EGFR tyrosine kinase inhibitor (TKI) and carried the T790M mutation and switched to osimertinib (Tagrisso) had “overwhelmingly” better response rates and progression-free survival, compared with patients put on standard-of-care chemotherapy in a multicenter randomized trial involving 419 patients, Vassiliki A. Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.
The AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3) trial enrolled 419 patients at 126 international sites during 2014 and 2015. The trial’s primary endpoint was investigator-assessed progression-free survival, which occurred after a median of 10.1 months with osimertinib and 4.4 months with standard chemotherapy, a statistically significant 70% relative risk reduction (P less than .001) in the hazard for death or progressive disease. The drug was as effective for patients with central nervous system metastases as it was for the other patients, which Dr. Papadimitrakopoulou attributed to osimertinib’s good penetration across the blood-brain barrier. The drug’s overall performance in AURA3 was completely consistent with the results of earlier studies that led to its U.S. approval.
Despite that approval, routine testing for T790M mutations and routine prescribing of osimertinib to positive patients “has not fully penetrated U.S. practice,” Dr. Papadimitrakopoulou said, but she hoped that these new confirmatory data will now firmly establish it as standard of care for the tested population.
Osimertinib is now under testing as first-line TKI treatment for EGFR-positive NSCLC regardless of the tumor’s T790M status. It’s going head to head with two first-generation EGFR TKIs, gefitinib and erlotinib, in the FLAURA trial, which should have reportable results in 2017. “We are very encouraged by the AURA3 data that osimertinib could beat the first-generation TKIs” for first-line treatment, she said.
AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Osimertinib overcomes the T790M mutation, which is the cause of about half of the non–small-cell lung cancers that are EGFR positive and develop resistance to a first- or-second generation tyrosine kinase inhibitor. The AURA3 results officially make osimertinib the standard of care for these patients.
Osimertinib’s performance in AURA3 was consistent with what it did in the earlier studies, producing an overall response rate of about 60%-70% and extending progression-free survival out to a median of 10-11 months.
Tetsuya Mitsudomi, MD, is professor of thoracic surgery at Kindai University in Osaka-Sayama, Japan. He has been a consultant to, and has received honoraria and research support from, AstraZeneca and several other companies. He was principal investigator for AURA2, one of the phase II studies of osimertinib. He made these comments as designated discussant for AURA3.
Osimertinib overcomes the T790M mutation, which is the cause of about half of the non–small-cell lung cancers that are EGFR positive and develop resistance to a first- or-second generation tyrosine kinase inhibitor. The AURA3 results officially make osimertinib the standard of care for these patients.
Osimertinib’s performance in AURA3 was consistent with what it did in the earlier studies, producing an overall response rate of about 60%-70% and extending progression-free survival out to a median of 10-11 months.
Tetsuya Mitsudomi, MD, is professor of thoracic surgery at Kindai University in Osaka-Sayama, Japan. He has been a consultant to, and has received honoraria and research support from, AstraZeneca and several other companies. He was principal investigator for AURA2, one of the phase II studies of osimertinib. He made these comments as designated discussant for AURA3.
Osimertinib overcomes the T790M mutation, which is the cause of about half of the non–small-cell lung cancers that are EGFR positive and develop resistance to a first- or-second generation tyrosine kinase inhibitor. The AURA3 results officially make osimertinib the standard of care for these patients.
Osimertinib’s performance in AURA3 was consistent with what it did in the earlier studies, producing an overall response rate of about 60%-70% and extending progression-free survival out to a median of 10-11 months.
Tetsuya Mitsudomi, MD, is professor of thoracic surgery at Kindai University in Osaka-Sayama, Japan. He has been a consultant to, and has received honoraria and research support from, AstraZeneca and several other companies. He was principal investigator for AURA2, one of the phase II studies of osimertinib. He made these comments as designated discussant for AURA3.
VIENNA – Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that received U.S. marketing approval in November 2015 as second-line treatment for selected patients with non–small-cell lung cancer based on phase II trial data, now has the pivotal-trial results that completely justify that action.
During a median follow-up of just over 8 months, patients who had progressed on their first-line EGFR tyrosine kinase inhibitor (TKI) and carried the T790M mutation and switched to osimertinib (Tagrisso) had “overwhelmingly” better response rates and progression-free survival, compared with patients put on standard-of-care chemotherapy in a multicenter randomized trial involving 419 patients, Vassiliki A. Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.
The AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3) trial enrolled 419 patients at 126 international sites during 2014 and 2015. The trial’s primary endpoint was investigator-assessed progression-free survival, which occurred after a median of 10.1 months with osimertinib and 4.4 months with standard chemotherapy, a statistically significant 70% relative risk reduction (P less than .001) in the hazard for death or progressive disease. The drug was as effective for patients with central nervous system metastases as it was for the other patients, which Dr. Papadimitrakopoulou attributed to osimertinib’s good penetration across the blood-brain barrier. The drug’s overall performance in AURA3 was completely consistent with the results of earlier studies that led to its U.S. approval.
Despite that approval, routine testing for T790M mutations and routine prescribing of osimertinib to positive patients “has not fully penetrated U.S. practice,” Dr. Papadimitrakopoulou said, but she hoped that these new confirmatory data will now firmly establish it as standard of care for the tested population.
Osimertinib is now under testing as first-line TKI treatment for EGFR-positive NSCLC regardless of the tumor’s T790M status. It’s going head to head with two first-generation EGFR TKIs, gefitinib and erlotinib, in the FLAURA trial, which should have reportable results in 2017. “We are very encouraged by the AURA3 data that osimertinib could beat the first-generation TKIs” for first-line treatment, she said.
AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that received U.S. marketing approval in November 2015 as second-line treatment for selected patients with non–small-cell lung cancer based on phase II trial data, now has the pivotal-trial results that completely justify that action.
During a median follow-up of just over 8 months, patients who had progressed on their first-line EGFR tyrosine kinase inhibitor (TKI) and carried the T790M mutation and switched to osimertinib (Tagrisso) had “overwhelmingly” better response rates and progression-free survival, compared with patients put on standard-of-care chemotherapy in a multicenter randomized trial involving 419 patients, Vassiliki A. Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.
The AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3) trial enrolled 419 patients at 126 international sites during 2014 and 2015. The trial’s primary endpoint was investigator-assessed progression-free survival, which occurred after a median of 10.1 months with osimertinib and 4.4 months with standard chemotherapy, a statistically significant 70% relative risk reduction (P less than .001) in the hazard for death or progressive disease. The drug was as effective for patients with central nervous system metastases as it was for the other patients, which Dr. Papadimitrakopoulou attributed to osimertinib’s good penetration across the blood-brain barrier. The drug’s overall performance in AURA3 was completely consistent with the results of earlier studies that led to its U.S. approval.
Despite that approval, routine testing for T790M mutations and routine prescribing of osimertinib to positive patients “has not fully penetrated U.S. practice,” Dr. Papadimitrakopoulou said, but she hoped that these new confirmatory data will now firmly establish it as standard of care for the tested population.
Osimertinib is now under testing as first-line TKI treatment for EGFR-positive NSCLC regardless of the tumor’s T790M status. It’s going head to head with two first-generation EGFR TKIs, gefitinib and erlotinib, in the FLAURA trial, which should have reportable results in 2017. “We are very encouraged by the AURA3 data that osimertinib could beat the first-generation TKIs” for first-line treatment, she said.
AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Key clinical point:
Major finding: Progression-free survival averaged 10.1 months with osimertinib and 4.4 months in patients on standard chemotherapy.
Data source: AURA3, which randomized 419 patients at 126 international centers.
Disclosures: AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
‘Vanishing’ role forecast for whole-brain irradiation for NSCLC metastases
VIENNA – Icotinib proved significantly more effective and less toxic than standard therapy with whole-brain irradiation and chemotherapy in patients with multiple brain metastases from epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer in the phase III BRAIN trial.
“With favorable objective response and disease control rates, icotinib was superior to whole-brain irradiation with chemotherapy, and therefore icotinib should be used as first-line therapy for advanced EGFR-mutant non–small cell lung cancers with brain metastases,” Yi-long Wu, MD, said in presenting the BRAIN results at the World Congress on Lung Cancer.
Patients with brain metastases are often excluded from participation in clinical trials because their prognosis is so poor. BRAIN is the first phase III trial to report results comparing an EGFR tyrosine kinase inhibitor (TKI) – icotinib – to whole-brain irradiation (WBI) plus chemotherapy, regarded in National Comprehensive Cancer Network guidelines as standard therapy in the setting of brain metastases from NSCLC, noted Dr. Wu of the Guangdong Lung Cancer Institute in Guangzhou, China.
BRAIN was a multicenter Chinese trial in which investigators randomized 158 patients with three or more brain metastases from EGFR-mutated NSCLC to oral icotinib at 125 mg t.i.d. or to WBI with four to six cycles of concurrent or sequential platinum-based chemotherapy.
Icotinib outperformed standard therapy with WBI plus chemotherapy on multiple efficacy endpoints. Median intracranial progression-free survival was 10 months with icotinib, compared with only 4.8 months in patients on WBI with chemotherapy. At 6 months, 72% of patients assigned to icotinib remained free of intracranial disease progression, compared with just 48% of controls on WBI and chemotherapy. Six-month overall PFS, intracranial as well as extracranial, was 6.8 months with icotinib and 3.4 months in the WBI group. The intracranial and overall objective response rates were 67% and 55%, respectively, with icotinib, compared with 41% and 11% with WBI.
In addition, the EGFR TKI had a significantly better safety profile: grade 3 or worse toxicities occurred in just 8% of the icotinib group, compared with 26% of controls on standard therapy, Dr. Wu reported at the meeting sponsored by the International Association for the Study of Lung Cancer.
There was, however, no significant difference between the two study arms in overall survival: 18 months with icotinib, 20.5 months with standard therapy, noted Dr. Wu, who is president of the Chinese Society of Clinical Oncology.
Discussant Jacek Jassem, MD, said “This is potentially, and likely, a practice-changing study.” He added that he’s looking forward to planned future presentation of neurotoxicity and quality of life data from BRAIN. Those important endpoints are also incorporated in the ongoing phase III trials of gefitinib and erlotinib, EGFR TKIs which are far more readily accessible at present to physicians outside the Far East.
“Whole-brain radiotherapy for brain metastases from EGFR-mutated non–small cell lung cancer is a vanishing approach. The remaining role in this setting is as salvage in cases of symptomatic primary or secondary resistance to EGFR TKIs,” said Dr. Jassem, head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
By way of background, he noted that 10%-15% of patients already have brain metastases at the time of diagnosis of NSCLC, and 40% develop them eventually. EGFR-mutated primary tumors are particularly likely to metastasize to the brain.
Remaining questions in the wake of the BRAIN trial include the efficacy of gefitinib and erlotinib versus WBI plus chemotherapy, as well as the broader question of the efficacy of EGFR TKIs in non-Asian patients with brain metastases.
“Most of the studies of EGFR TKIs have been in East Asian populations. These agents are particularly active in East Asians. There’s a question as to whether the BRAIN results can be applied to other populations,” Dr. Jassem said.
The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi. Dr. Jassem reported having no financial conflicts of interest.
VIENNA – Icotinib proved significantly more effective and less toxic than standard therapy with whole-brain irradiation and chemotherapy in patients with multiple brain metastases from epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer in the phase III BRAIN trial.
“With favorable objective response and disease control rates, icotinib was superior to whole-brain irradiation with chemotherapy, and therefore icotinib should be used as first-line therapy for advanced EGFR-mutant non–small cell lung cancers with brain metastases,” Yi-long Wu, MD, said in presenting the BRAIN results at the World Congress on Lung Cancer.
Patients with brain metastases are often excluded from participation in clinical trials because their prognosis is so poor. BRAIN is the first phase III trial to report results comparing an EGFR tyrosine kinase inhibitor (TKI) – icotinib – to whole-brain irradiation (WBI) plus chemotherapy, regarded in National Comprehensive Cancer Network guidelines as standard therapy in the setting of brain metastases from NSCLC, noted Dr. Wu of the Guangdong Lung Cancer Institute in Guangzhou, China.
BRAIN was a multicenter Chinese trial in which investigators randomized 158 patients with three or more brain metastases from EGFR-mutated NSCLC to oral icotinib at 125 mg t.i.d. or to WBI with four to six cycles of concurrent or sequential platinum-based chemotherapy.
Icotinib outperformed standard therapy with WBI plus chemotherapy on multiple efficacy endpoints. Median intracranial progression-free survival was 10 months with icotinib, compared with only 4.8 months in patients on WBI with chemotherapy. At 6 months, 72% of patients assigned to icotinib remained free of intracranial disease progression, compared with just 48% of controls on WBI and chemotherapy. Six-month overall PFS, intracranial as well as extracranial, was 6.8 months with icotinib and 3.4 months in the WBI group. The intracranial and overall objective response rates were 67% and 55%, respectively, with icotinib, compared with 41% and 11% with WBI.
In addition, the EGFR TKI had a significantly better safety profile: grade 3 or worse toxicities occurred in just 8% of the icotinib group, compared with 26% of controls on standard therapy, Dr. Wu reported at the meeting sponsored by the International Association for the Study of Lung Cancer.
There was, however, no significant difference between the two study arms in overall survival: 18 months with icotinib, 20.5 months with standard therapy, noted Dr. Wu, who is president of the Chinese Society of Clinical Oncology.
Discussant Jacek Jassem, MD, said “This is potentially, and likely, a practice-changing study.” He added that he’s looking forward to planned future presentation of neurotoxicity and quality of life data from BRAIN. Those important endpoints are also incorporated in the ongoing phase III trials of gefitinib and erlotinib, EGFR TKIs which are far more readily accessible at present to physicians outside the Far East.
“Whole-brain radiotherapy for brain metastases from EGFR-mutated non–small cell lung cancer is a vanishing approach. The remaining role in this setting is as salvage in cases of symptomatic primary or secondary resistance to EGFR TKIs,” said Dr. Jassem, head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
By way of background, he noted that 10%-15% of patients already have brain metastases at the time of diagnosis of NSCLC, and 40% develop them eventually. EGFR-mutated primary tumors are particularly likely to metastasize to the brain.
Remaining questions in the wake of the BRAIN trial include the efficacy of gefitinib and erlotinib versus WBI plus chemotherapy, as well as the broader question of the efficacy of EGFR TKIs in non-Asian patients with brain metastases.
“Most of the studies of EGFR TKIs have been in East Asian populations. These agents are particularly active in East Asians. There’s a question as to whether the BRAIN results can be applied to other populations,” Dr. Jassem said.
The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi. Dr. Jassem reported having no financial conflicts of interest.
VIENNA – Icotinib proved significantly more effective and less toxic than standard therapy with whole-brain irradiation and chemotherapy in patients with multiple brain metastases from epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer in the phase III BRAIN trial.
“With favorable objective response and disease control rates, icotinib was superior to whole-brain irradiation with chemotherapy, and therefore icotinib should be used as first-line therapy for advanced EGFR-mutant non–small cell lung cancers with brain metastases,” Yi-long Wu, MD, said in presenting the BRAIN results at the World Congress on Lung Cancer.
Patients with brain metastases are often excluded from participation in clinical trials because their prognosis is so poor. BRAIN is the first phase III trial to report results comparing an EGFR tyrosine kinase inhibitor (TKI) – icotinib – to whole-brain irradiation (WBI) plus chemotherapy, regarded in National Comprehensive Cancer Network guidelines as standard therapy in the setting of brain metastases from NSCLC, noted Dr. Wu of the Guangdong Lung Cancer Institute in Guangzhou, China.
BRAIN was a multicenter Chinese trial in which investigators randomized 158 patients with three or more brain metastases from EGFR-mutated NSCLC to oral icotinib at 125 mg t.i.d. or to WBI with four to six cycles of concurrent or sequential platinum-based chemotherapy.
Icotinib outperformed standard therapy with WBI plus chemotherapy on multiple efficacy endpoints. Median intracranial progression-free survival was 10 months with icotinib, compared with only 4.8 months in patients on WBI with chemotherapy. At 6 months, 72% of patients assigned to icotinib remained free of intracranial disease progression, compared with just 48% of controls on WBI and chemotherapy. Six-month overall PFS, intracranial as well as extracranial, was 6.8 months with icotinib and 3.4 months in the WBI group. The intracranial and overall objective response rates were 67% and 55%, respectively, with icotinib, compared with 41% and 11% with WBI.
In addition, the EGFR TKI had a significantly better safety profile: grade 3 or worse toxicities occurred in just 8% of the icotinib group, compared with 26% of controls on standard therapy, Dr. Wu reported at the meeting sponsored by the International Association for the Study of Lung Cancer.
There was, however, no significant difference between the two study arms in overall survival: 18 months with icotinib, 20.5 months with standard therapy, noted Dr. Wu, who is president of the Chinese Society of Clinical Oncology.
Discussant Jacek Jassem, MD, said “This is potentially, and likely, a practice-changing study.” He added that he’s looking forward to planned future presentation of neurotoxicity and quality of life data from BRAIN. Those important endpoints are also incorporated in the ongoing phase III trials of gefitinib and erlotinib, EGFR TKIs which are far more readily accessible at present to physicians outside the Far East.
“Whole-brain radiotherapy for brain metastases from EGFR-mutated non–small cell lung cancer is a vanishing approach. The remaining role in this setting is as salvage in cases of symptomatic primary or secondary resistance to EGFR TKIs,” said Dr. Jassem, head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
By way of background, he noted that 10%-15% of patients already have brain metastases at the time of diagnosis of NSCLC, and 40% develop them eventually. EGFR-mutated primary tumors are particularly likely to metastasize to the brain.
Remaining questions in the wake of the BRAIN trial include the efficacy of gefitinib and erlotinib versus WBI plus chemotherapy, as well as the broader question of the efficacy of EGFR TKIs in non-Asian patients with brain metastases.
“Most of the studies of EGFR TKIs have been in East Asian populations. These agents are particularly active in East Asians. There’s a question as to whether the BRAIN results can be applied to other populations,” Dr. Jassem said.
The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi. Dr. Jassem reported having no financial conflicts of interest.
AT WCLC 2016
Key clinical point:
Major finding: Median intracranial progression-free survival in patients with multiple brain metastases from EGFR-mutated NSCLC was 10 months in those randomized to icotinib, compared with 4.8 months with standard-of-care whole-brain irradiation plus chemotherapy.
Data source: This phase III multicenter Chinese trial included 158 patients with multiple brain metastases from EGFR-mutated NSCLC.
Disclosures: The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. The presenter reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi.
Ganetespib fails to hit mark in phase III NSCLC trial
VIENNA – The addition of ganetespib to docetaxel for the treatment of advanced non–small cell lung cancer (NSCLC) did not live up to its earlier promise of improved efficacy over docetaxel alone in a phase III study.
Interim results of the GALAXY-2 study, which led to the trial’s termination for futility, showed that there was no difference in the primary endpoint of overall survival (OS). The median OS was a respective 10.9 months and 10.5 months for the combination of ganetespib plus docetaxel versus docetaxel alone (hazard ratio, 1.111, 95% confidence interval, 0.899-1.372, P = .03293).
The combination had looked promising in the phase II GALAXY-1 study (Ann Oncol. 2015;26:1741-8), with a trend towards improved PFS and OS, with patients diagnosed with advanced disease perhaps gaining the most benefit.
“The addition of ganetespib to docetaxel did not result in improved efficacy for the salvage therapy of patients with advanced-stage lung adenocarcinoma,” Rathi Pillai, MD, said at the World Conference on Lung Cancer.
“Based on these findings, further development of Hsp [heat shock protein] 90 inhibitors in lung cancer should be limited to patients with driver mutations with relevant client proteins,” added Dr. Pillai of the Winship Cancer Institute at Emory University in Atlanta.
In GALAXY-2, 672 patients were randomized, 1:1, to receive docetaxel (75 mg/m2 on day 1) with ganetespib (150 mg/m2 on days 1 and 15) or a placebo every 3 weeks. The median number of cycles received was five in the combination arm and four in the docetaxel-only arm. All patients had advanced non–small cell lung adenocarcinoma diagnosed at least 6 months prior to enrollment and had received only one prior treatment regimen.
Response rates were similar between the two groups, with 13.7% and 16% of ganetespib/docetaxel– and docetaxel/placebo–treated patients achieving a partial response (P = .448) and 56.1% and 50.1%, respectively, having stable disease (P = .123).
Almost two-thirds (65%) of patients given ganetespib/docetaxel reported any grade 3-4 adverse event versus 54% of patients given docetaxel/placebo. The most frequent treatment-emergent grade 3-4 adverse event was neutropenia, occurring in 34.6% ad 29.5% of patients in each arm (P = .1807), with only diarrhea (46.2% vs. 14.6%; P less than .0001) and weight loss (11.3% vs. 5.2%; P = .0044) occurring more frequently in the combination than the docetaxel-only arm.
Ganetespib is a second-generation Hsp90 inhibitor and the rationale for using Hsp90 inhibitors as cancer therapy remains sound, Dr. Gandara maintained. One of the issues is finding a biomarker to predict the benefit for these drugs in a clinical setting, he said. In the phase II GALAXY-1 trial it was noted that patients diagnosed with advanced disease more than 6 months prior to study entry fared better than those with more recent diagnosis if they were treated with ganetespib/docetaxel than docetaxel alone. Patients with elevated levels of lactate dehydrogenase (eLDH) also seemed to do better than those with normal LDH levels if they were treated with the combination.
These two subpopulations were specifically looked at the in the phase III study, but again no differences in OS or PFS were observed, nor were differences observed in any of the other subgroups analyzed, which included EGFR- and ALK-negative patients, by response rate or progression because of new metastatic lesions.
“Were these the right surrogates to use as predictive biomarkers for heat shock protein inhibition? Of course, in retrospect, it is easy to say that they were not,” Dr. Gandara said.
“Is there still an opportunity for this class of drugs to make a meaningful impact in NSCLC? In my own opinion I think the answer is yes, but not in this broad page approach and not with these potential surrogates as were used in GALAXY-2,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.
The study was sponsored by Synta Pharmaceuticals, which became part of Madrigal Pharmaceuticals in June 2016. Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.
VIENNA – The addition of ganetespib to docetaxel for the treatment of advanced non–small cell lung cancer (NSCLC) did not live up to its earlier promise of improved efficacy over docetaxel alone in a phase III study.
Interim results of the GALAXY-2 study, which led to the trial’s termination for futility, showed that there was no difference in the primary endpoint of overall survival (OS). The median OS was a respective 10.9 months and 10.5 months for the combination of ganetespib plus docetaxel versus docetaxel alone (hazard ratio, 1.111, 95% confidence interval, 0.899-1.372, P = .03293).
The combination had looked promising in the phase II GALAXY-1 study (Ann Oncol. 2015;26:1741-8), with a trend towards improved PFS and OS, with patients diagnosed with advanced disease perhaps gaining the most benefit.
“The addition of ganetespib to docetaxel did not result in improved efficacy for the salvage therapy of patients with advanced-stage lung adenocarcinoma,” Rathi Pillai, MD, said at the World Conference on Lung Cancer.
“Based on these findings, further development of Hsp [heat shock protein] 90 inhibitors in lung cancer should be limited to patients with driver mutations with relevant client proteins,” added Dr. Pillai of the Winship Cancer Institute at Emory University in Atlanta.
In GALAXY-2, 672 patients were randomized, 1:1, to receive docetaxel (75 mg/m2 on day 1) with ganetespib (150 mg/m2 on days 1 and 15) or a placebo every 3 weeks. The median number of cycles received was five in the combination arm and four in the docetaxel-only arm. All patients had advanced non–small cell lung adenocarcinoma diagnosed at least 6 months prior to enrollment and had received only one prior treatment regimen.
Response rates were similar between the two groups, with 13.7% and 16% of ganetespib/docetaxel– and docetaxel/placebo–treated patients achieving a partial response (P = .448) and 56.1% and 50.1%, respectively, having stable disease (P = .123).
Almost two-thirds (65%) of patients given ganetespib/docetaxel reported any grade 3-4 adverse event versus 54% of patients given docetaxel/placebo. The most frequent treatment-emergent grade 3-4 adverse event was neutropenia, occurring in 34.6% ad 29.5% of patients in each arm (P = .1807), with only diarrhea (46.2% vs. 14.6%; P less than .0001) and weight loss (11.3% vs. 5.2%; P = .0044) occurring more frequently in the combination than the docetaxel-only arm.
Ganetespib is a second-generation Hsp90 inhibitor and the rationale for using Hsp90 inhibitors as cancer therapy remains sound, Dr. Gandara maintained. One of the issues is finding a biomarker to predict the benefit for these drugs in a clinical setting, he said. In the phase II GALAXY-1 trial it was noted that patients diagnosed with advanced disease more than 6 months prior to study entry fared better than those with more recent diagnosis if they were treated with ganetespib/docetaxel than docetaxel alone. Patients with elevated levels of lactate dehydrogenase (eLDH) also seemed to do better than those with normal LDH levels if they were treated with the combination.
These two subpopulations were specifically looked at the in the phase III study, but again no differences in OS or PFS were observed, nor were differences observed in any of the other subgroups analyzed, which included EGFR- and ALK-negative patients, by response rate or progression because of new metastatic lesions.
“Were these the right surrogates to use as predictive biomarkers for heat shock protein inhibition? Of course, in retrospect, it is easy to say that they were not,” Dr. Gandara said.
“Is there still an opportunity for this class of drugs to make a meaningful impact in NSCLC? In my own opinion I think the answer is yes, but not in this broad page approach and not with these potential surrogates as were used in GALAXY-2,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.
The study was sponsored by Synta Pharmaceuticals, which became part of Madrigal Pharmaceuticals in June 2016. Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.
VIENNA – The addition of ganetespib to docetaxel for the treatment of advanced non–small cell lung cancer (NSCLC) did not live up to its earlier promise of improved efficacy over docetaxel alone in a phase III study.
Interim results of the GALAXY-2 study, which led to the trial’s termination for futility, showed that there was no difference in the primary endpoint of overall survival (OS). The median OS was a respective 10.9 months and 10.5 months for the combination of ganetespib plus docetaxel versus docetaxel alone (hazard ratio, 1.111, 95% confidence interval, 0.899-1.372, P = .03293).
The combination had looked promising in the phase II GALAXY-1 study (Ann Oncol. 2015;26:1741-8), with a trend towards improved PFS and OS, with patients diagnosed with advanced disease perhaps gaining the most benefit.
“The addition of ganetespib to docetaxel did not result in improved efficacy for the salvage therapy of patients with advanced-stage lung adenocarcinoma,” Rathi Pillai, MD, said at the World Conference on Lung Cancer.
“Based on these findings, further development of Hsp [heat shock protein] 90 inhibitors in lung cancer should be limited to patients with driver mutations with relevant client proteins,” added Dr. Pillai of the Winship Cancer Institute at Emory University in Atlanta.
In GALAXY-2, 672 patients were randomized, 1:1, to receive docetaxel (75 mg/m2 on day 1) with ganetespib (150 mg/m2 on days 1 and 15) or a placebo every 3 weeks. The median number of cycles received was five in the combination arm and four in the docetaxel-only arm. All patients had advanced non–small cell lung adenocarcinoma diagnosed at least 6 months prior to enrollment and had received only one prior treatment regimen.
Response rates were similar between the two groups, with 13.7% and 16% of ganetespib/docetaxel– and docetaxel/placebo–treated patients achieving a partial response (P = .448) and 56.1% and 50.1%, respectively, having stable disease (P = .123).
Almost two-thirds (65%) of patients given ganetespib/docetaxel reported any grade 3-4 adverse event versus 54% of patients given docetaxel/placebo. The most frequent treatment-emergent grade 3-4 adverse event was neutropenia, occurring in 34.6% ad 29.5% of patients in each arm (P = .1807), with only diarrhea (46.2% vs. 14.6%; P less than .0001) and weight loss (11.3% vs. 5.2%; P = .0044) occurring more frequently in the combination than the docetaxel-only arm.
Ganetespib is a second-generation Hsp90 inhibitor and the rationale for using Hsp90 inhibitors as cancer therapy remains sound, Dr. Gandara maintained. One of the issues is finding a biomarker to predict the benefit for these drugs in a clinical setting, he said. In the phase II GALAXY-1 trial it was noted that patients diagnosed with advanced disease more than 6 months prior to study entry fared better than those with more recent diagnosis if they were treated with ganetespib/docetaxel than docetaxel alone. Patients with elevated levels of lactate dehydrogenase (eLDH) also seemed to do better than those with normal LDH levels if they were treated with the combination.
These two subpopulations were specifically looked at the in the phase III study, but again no differences in OS or PFS were observed, nor were differences observed in any of the other subgroups analyzed, which included EGFR- and ALK-negative patients, by response rate or progression because of new metastatic lesions.
“Were these the right surrogates to use as predictive biomarkers for heat shock protein inhibition? Of course, in retrospect, it is easy to say that they were not,” Dr. Gandara said.
“Is there still an opportunity for this class of drugs to make a meaningful impact in NSCLC? In my own opinion I think the answer is yes, but not in this broad page approach and not with these potential surrogates as were used in GALAXY-2,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.
The study was sponsored by Synta Pharmaceuticals, which became part of Madrigal Pharmaceuticals in June 2016. Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.
AT WCLC 2016
Key clinical point: Adding ganetespib to docetaxel did not improve the survival of the patients studied versus docetaxel alone.
Major finding: Median overall survival was 10.9 months for ganetespib/docetaxel and 10.5 months for docetaxel alone (HR, 1.111; 95% CI, 0.899-1.372; P = .03293).
Data source: International, randomized, phase III, open-label GALAXY-2 study of docetaxel with or without ganetespib in 672 patients with advanced non–small cell lung adenocarcinoma.
Disclosures: The study was sponsored by Synta Pharmaceuticals (Madrigal Pharmaceuticals since June 2016). Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.