Pembrolizumab monotherapy posts 6.75-month PFS in stage IV NSCLC

CHICAGO – Monotherapy with the experimental anti-PD-1 antibody pembrolizumab induced durable treatment responses and slowed progression 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 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 enrolled 84 previously untreated patients with stage IV NSCLC and an Eastern Cooperative Oncology Group (ECOG) 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.

Patients received a median of nine doses (range 1-23) and spent an average of 154 days on therapy (range 1-400).

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.

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.

Grade 1-2 treatment-related events occurred in 36 of the 45 patients. The most common events were fatigue in 10 patients, pruritus in 6, and hypothyroidism in 4.

There was one each treatment-related grade 4 blood creatine phosphokinase elevation, grade 3 pericardial effusion, grade 3 pneumonitis, and grade 2 kidney injury, with two events leading to treatment discontinuation.

"Based on these safety data, we feel pembrolizumab is a safe and well-tolerated regimen," Dr. Rizvi said.

An additional 50 patients are being enrolled in the KEYNOTE-001 study, with the total population to be analyzed both with 1% and 45% cut points, he 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.

[email protected]

CHICAGO – Monotherapy with the experimental anti-PD-1 antibody pembrolizumab induced durable treatment responses and slowed progression 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 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 enrolled 84 previously untreated patients with stage IV NSCLC and an Eastern Cooperative Oncology Group (ECOG) 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.

Patients received a median of nine doses (range 1-23) and spent an average of 154 days on therapy (range 1-400).

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.

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.

Grade 1-2 treatment-related events occurred in 36 of the 45 patients. The most common events were fatigue in 10 patients, pruritus in 6, and hypothyroidism in 4.

There was one each treatment-related grade 4 blood creatine phosphokinase elevation, grade 3 pericardial effusion, grade 3 pneumonitis, and grade 2 kidney injury, with two events leading to treatment discontinuation.

"Based on these safety data, we feel pembrolizumab is a safe and well-tolerated regimen," Dr. Rizvi said.

An additional 50 patients are being enrolled in the KEYNOTE-001 study, with the total population to be analyzed both with 1% and 45% cut points, he 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.

[email protected]

CHICAGO – Monotherapy with the experimental anti-PD-1 antibody pembrolizumab induced durable treatment responses and slowed progression 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 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 enrolled 84 previously untreated patients with stage IV NSCLC and an Eastern Cooperative Oncology Group (ECOG) 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.

Patients received a median of nine doses (range 1-23) and spent an average of 154 days on therapy (range 1-400).

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.

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.

Grade 1-2 treatment-related events occurred in 36 of the 45 patients. The most common events were fatigue in 10 patients, pruritus in 6, and hypothyroidism in 4.

There was one each treatment-related grade 4 blood creatine phosphokinase elevation, grade 3 pericardial effusion, grade 3 pneumonitis, and grade 2 kidney injury, with two events leading to treatment discontinuation.

"Based on these safety data, we feel pembrolizumab is a safe and well-tolerated regimen," Dr. Rizvi said.

An additional 50 patients are being enrolled in the KEYNOTE-001 study, with the total population to be analyzed both with 1% and 45% cut points, he 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.

[email protected]