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CHICAGO – Monotherapy with the experimental anti-PD-1 antibody pembrolizumab induced durable treatment responses and improved progression-free survival in previously untreated stage IV non–small cell lung cancer in an ongoing phase Ib trial.
The overall response rate was 26% (11 of 42 patients) by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and 47% (21 of 45 patients) by investigator-assessed, immune-related response criteria (irRC).
Responses are ongoing in 100% of responders by RECIST and 90% of responders by irRC, with the median duration of response not reached after a median of 36 weeks’ follow-up, Dr. Naiyer Rizvi said at the annual meeting of the American Society of Clinical Oncology.
Responses in the phase I KEYNOTE-001 study are very comparable with response rates of 15%-32% achieved with classic chemotherapy in the first-line setting in phase III studies using gemcitabine plus cisplatin, taxol plus carboplatin, or pemetrexed plus cisplatin, said invited discussant Dr. Julie Brahmer of Johns Hopkins University, Baltimore.
"The key thing [with pembrolizumab] is that these responses are very long lasting," she said.
Moreover, median progression-free survival (PFS) with the classic chemotherapy doublets ranged from 4.5 months to 5.3 months but reached 6.75 months by RECIST and 9.25 months by irRC in the interim analysis of pembrolizumab.
"A very early but interesting progression-free survival of 6.75 months is quite intriguing," Dr. Brahmer said.
Enrollment is expected to begin this September in the phase III KEYNOTE-024 study comparing pembrolizumab monotherapy with platinum-based doublet chemotherapy in treatment-naive PD-L1 positive, metastatic non–small cell lung cancer (NSCLC), said Dr. Rizvi, a medical oncologist with Memorial Sloan Kettering Cancer Center in New York.
Study details
Pembrolizumab, previously known as MK-3475, exerts dual ligand (PD-L1 and PD-L2) blockade of the programmed death 1 (PD-1) pathway. It is being investigated in more than 30 different cancers, and it made waves at the ASCO meeting for its treatment of metastatic melanoma.
Dr. Brahmer said that the key questions for the current study are whether PD-L1 sensitivity was the right biomarker to use and what the best cut-off is.
The KEYNOTE-001 study (clinicaltrials.gov/ show/NCT01295827) http://abstracts.asco.org/144/AbstView_144_132675.html enrolled 84 previously untreated patients with stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1. Tumors were classified as PD-L1 positive in 57 patients, using a cut point of at least 1% of tumor cells stained, as measured using a prototype immunohistochemistry assay.
Of these 57 patients, 45 with evaluable imaging at baseline were randomly assigned to pembrolizumab 10 mg/kg every 3 weeks or 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Most patients (76%) had nonsquamous histology, and 69% were former smokers.
Tumor shrinkage by RECIST criteria occurred in 80% of patients with measurable disease and at least one postbaseline scan, Dr. Rizvi said. Activity was observed across dose levels and across the 2- and 3-week schedules.
Safety data indicate the regimen is "safe and well tolerated," Dr. Rizvi said.
Nine patients with new tumors would have been considered as having progressive disease and likely taken off therapy if they had been assessed by traditional RECIST criteria rather than irRC, "illustrating that RECIST may not be the best imaging modality to assess patients treated with immunotherapy," he said.
Safety data indicate the regimen is "safe and well-tolerated," Dr. Rizvi said.
The study was supported by Merck. Dr. Rizvi reported a consultant or advisory role with Bristol-Myers Squibb and honoraria from Bristol-Myers Squibb, MedImmune, and Roche/Genentech.
Dr. Lary Robinson, FCCP, comments:
In this dose-escalation phase Ib safety trial of pembrolizumab used alone in 45 stage IV NSCLC treatment-naive patients whose tumor expresses PD-L1, there was an intriguing 26%-47% response with a 6.75- to 9.25-month median progression-free survival (depending on response criteria used) with only mild toxicity, which is far better than the classic doublet chemotherapy response.
Further trials of these agents should prove whether this novel immunotherapy approach to systemic treatment of lung cancer is potentially a breakthrough in treatment, that soon may become the preferred first-line, well-tolerated therapy for this very large group of metastatic lung cancer patients who express high levels of PD-L1.
Dr. Lary Robinson, FCCP, comments:
In this dose-escalation phase Ib safety trial of pembrolizumab used alone in 45 stage IV NSCLC treatment-naive patients whose tumor expresses PD-L1, there was an intriguing 26%-47% response with a 6.75- to 9.25-month median progression-free survival (depending on response criteria used) with only mild toxicity, which is far better than the classic doublet chemotherapy response.
Further trials of these agents should prove whether this novel immunotherapy approach to systemic treatment of lung cancer is potentially a breakthrough in treatment, that soon may become the preferred first-line, well-tolerated therapy for this very large group of metastatic lung cancer patients who express high levels of PD-L1.
Dr. Lary Robinson, FCCP, comments:
In this dose-escalation phase Ib safety trial of pembrolizumab used alone in 45 stage IV NSCLC treatment-naive patients whose tumor expresses PD-L1, there was an intriguing 26%-47% response with a 6.75- to 9.25-month median progression-free survival (depending on response criteria used) with only mild toxicity, which is far better than the classic doublet chemotherapy response.
Further trials of these agents should prove whether this novel immunotherapy approach to systemic treatment of lung cancer is potentially a breakthrough in treatment, that soon may become the preferred first-line, well-tolerated therapy for this very large group of metastatic lung cancer patients who express high levels of PD-L1.
CHICAGO – Monotherapy with the experimental anti-PD-1 antibody pembrolizumab induced durable treatment responses and improved progression-free survival in previously untreated stage IV non–small cell lung cancer in an ongoing phase Ib trial.
The overall response rate was 26% (11 of 42 patients) by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and 47% (21 of 45 patients) by investigator-assessed, immune-related response criteria (irRC).
Responses are ongoing in 100% of responders by RECIST and 90% of responders by irRC, with the median duration of response not reached after a median of 36 weeks’ follow-up, Dr. Naiyer Rizvi said at the annual meeting of the American Society of Clinical Oncology.
Responses in the phase I KEYNOTE-001 study are very comparable with response rates of 15%-32% achieved with classic chemotherapy in the first-line setting in phase III studies using gemcitabine plus cisplatin, taxol plus carboplatin, or pemetrexed plus cisplatin, said invited discussant Dr. Julie Brahmer of Johns Hopkins University, Baltimore.
"The key thing [with pembrolizumab] is that these responses are very long lasting," she said.
Moreover, median progression-free survival (PFS) with the classic chemotherapy doublets ranged from 4.5 months to 5.3 months but reached 6.75 months by RECIST and 9.25 months by irRC in the interim analysis of pembrolizumab.
"A very early but interesting progression-free survival of 6.75 months is quite intriguing," Dr. Brahmer said.
Enrollment is expected to begin this September in the phase III KEYNOTE-024 study comparing pembrolizumab monotherapy with platinum-based doublet chemotherapy in treatment-naive PD-L1 positive, metastatic non–small cell lung cancer (NSCLC), said Dr. Rizvi, a medical oncologist with Memorial Sloan Kettering Cancer Center in New York.
Study details
Pembrolizumab, previously known as MK-3475, exerts dual ligand (PD-L1 and PD-L2) blockade of the programmed death 1 (PD-1) pathway. It is being investigated in more than 30 different cancers, and it made waves at the ASCO meeting for its treatment of metastatic melanoma.
Dr. Brahmer said that the key questions for the current study are whether PD-L1 sensitivity was the right biomarker to use and what the best cut-off is.
The KEYNOTE-001 study (clinicaltrials.gov/ show/NCT01295827) http://abstracts.asco.org/144/AbstView_144_132675.html enrolled 84 previously untreated patients with stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1. Tumors were classified as PD-L1 positive in 57 patients, using a cut point of at least 1% of tumor cells stained, as measured using a prototype immunohistochemistry assay.
Of these 57 patients, 45 with evaluable imaging at baseline were randomly assigned to pembrolizumab 10 mg/kg every 3 weeks or 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Most patients (76%) had nonsquamous histology, and 69% were former smokers.
Tumor shrinkage by RECIST criteria occurred in 80% of patients with measurable disease and at least one postbaseline scan, Dr. Rizvi said. Activity was observed across dose levels and across the 2- and 3-week schedules.
Safety data indicate the regimen is "safe and well tolerated," Dr. Rizvi said.
Nine patients with new tumors would have been considered as having progressive disease and likely taken off therapy if they had been assessed by traditional RECIST criteria rather than irRC, "illustrating that RECIST may not be the best imaging modality to assess patients treated with immunotherapy," he said.
Safety data indicate the regimen is "safe and well-tolerated," Dr. Rizvi said.
The study was supported by Merck. Dr. Rizvi reported a consultant or advisory role with Bristol-Myers Squibb and honoraria from Bristol-Myers Squibb, MedImmune, and Roche/Genentech.
CHICAGO – Monotherapy with the experimental anti-PD-1 antibody pembrolizumab induced durable treatment responses and improved progression-free survival in previously untreated stage IV non–small cell lung cancer in an ongoing phase Ib trial.
The overall response rate was 26% (11 of 42 patients) by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and 47% (21 of 45 patients) by investigator-assessed, immune-related response criteria (irRC).
Responses are ongoing in 100% of responders by RECIST and 90% of responders by irRC, with the median duration of response not reached after a median of 36 weeks’ follow-up, Dr. Naiyer Rizvi said at the annual meeting of the American Society of Clinical Oncology.
Responses in the phase I KEYNOTE-001 study are very comparable with response rates of 15%-32% achieved with classic chemotherapy in the first-line setting in phase III studies using gemcitabine plus cisplatin, taxol plus carboplatin, or pemetrexed plus cisplatin, said invited discussant Dr. Julie Brahmer of Johns Hopkins University, Baltimore.
"The key thing [with pembrolizumab] is that these responses are very long lasting," she said.
Moreover, median progression-free survival (PFS) with the classic chemotherapy doublets ranged from 4.5 months to 5.3 months but reached 6.75 months by RECIST and 9.25 months by irRC in the interim analysis of pembrolizumab.
"A very early but interesting progression-free survival of 6.75 months is quite intriguing," Dr. Brahmer said.
Enrollment is expected to begin this September in the phase III KEYNOTE-024 study comparing pembrolizumab monotherapy with platinum-based doublet chemotherapy in treatment-naive PD-L1 positive, metastatic non–small cell lung cancer (NSCLC), said Dr. Rizvi, a medical oncologist with Memorial Sloan Kettering Cancer Center in New York.
Study details
Pembrolizumab, previously known as MK-3475, exerts dual ligand (PD-L1 and PD-L2) blockade of the programmed death 1 (PD-1) pathway. It is being investigated in more than 30 different cancers, and it made waves at the ASCO meeting for its treatment of metastatic melanoma.
Dr. Brahmer said that the key questions for the current study are whether PD-L1 sensitivity was the right biomarker to use and what the best cut-off is.
The KEYNOTE-001 study (clinicaltrials.gov/ show/NCT01295827) http://abstracts.asco.org/144/AbstView_144_132675.html enrolled 84 previously untreated patients with stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1. Tumors were classified as PD-L1 positive in 57 patients, using a cut point of at least 1% of tumor cells stained, as measured using a prototype immunohistochemistry assay.
Of these 57 patients, 45 with evaluable imaging at baseline were randomly assigned to pembrolizumab 10 mg/kg every 3 weeks or 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Most patients (76%) had nonsquamous histology, and 69% were former smokers.
Tumor shrinkage by RECIST criteria occurred in 80% of patients with measurable disease and at least one postbaseline scan, Dr. Rizvi said. Activity was observed across dose levels and across the 2- and 3-week schedules.
Safety data indicate the regimen is "safe and well tolerated," Dr. Rizvi said.
Nine patients with new tumors would have been considered as having progressive disease and likely taken off therapy if they had been assessed by traditional RECIST criteria rather than irRC, "illustrating that RECIST may not be the best imaging modality to assess patients treated with immunotherapy," he said.
Safety data indicate the regimen is "safe and well-tolerated," Dr. Rizvi said.
The study was supported by Merck. Dr. Rizvi reported a consultant or advisory role with Bristol-Myers Squibb and honoraria from Bristol-Myers Squibb, MedImmune, and Roche/Genentech.
Key clinical point: Median progression-free survival with the classic chemotherapy doublets ranged from 4.5 months to 5.3 months but reached 6.75 months by RECIST and 9.25 months by irRC in the interim analysis of pembrolizumab.
Major finding: The overall response rate was 26% by RECIST criteria and 47% by investigator-assessed, immune-related response criteria.
Data source: An ongoing phase 1b study in 45 patients with previously untreated advanced NSCLC.
Disclosures: The study was supported by Merck. Dr. Rizvi reported a consultant or advisory role with Bristol-Myers Squibb and honoraria from Bristol-Myers Squibb, MedImmune, and Roche/Genentech.