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Maintenance pembrolizumab benefits certain patients with small cell lung cancer

CHICAGO – Improvements in OS, but not PFS, indicate that maintenance treatment with pembrolizumab may benefit a subset of patients with small cell lung cancer, and biomarkers are needed to identify individuals in whom pembrolizumab may be effective, according to findings presented at the ASCO Annual Meeting.

“The standard of care for these patients – 4 to 6 cycles of platinum plus etoposide – has not changed in the United States in the last 30 years,” Shirish Gadgeel, MD, of the Karmanos Cancer Institute in Detroit, said during a presentation. “Despite a high response rate with this therapy, overall outcomes for these patients are quite poor. There is a need to identify other agents that can provide benefit in these patients.”

Gadgeel and colleagues enrolled patients with extensive-stage small cell lung cancer who had received 4 to 6 cycles of platinum plus etoposide and had either responded to therapy or had stable disease. Participants were required to start treatment with pembrolizumab within 8 weeks of finishing chemotherapy; restaging scans were conducted no more than 3 weeks before beginning pembrolizumab. Prophylactic cranial radiation was allowed.

Participants received 200 mg IV pembrolizumab every 3 weeks for a maximum duration of 2 years. The researchers performed disease assessments every 2 cycles throughout the first 6 cycles; future evaluations were guided by investigator choice.

The primary outcome of the study was PFS. PFS according to immune-related response criteria and OS were also evaluated.

The researchers examined tumor tissue for PD-L1 expression via the DAKO 22CE antibody and classified expression at any level as positive for PD-L1. Blood for circulating tumor cells was drawn before the first, second and third cycles of pembrolizumab.

Gadgeel and colleagues enrolled 45 patients. Slightly more than half (55%) were men and 22% had brain metastases. The median age of patients was 66 years.

Median time from completion of chemotherapy to initiation of pembrolizumab was 5 weeks. Patients were treated with a median of 4 cycles of pembrolizumab (range, 1-20). Most patients (n = 35) had measurable disease at the time of study entry.

The rate of disease control seen with pembrolizumab was 42%. One patient had a complete response; three achieved a partial response and 15 had stable disease.

Median PFS at the median follow-up point of 6 months was 1.4 months (90% CI, 1.3-4.0). The PFS according to immune-related response criteria was 4.7 months (90% CI, 1.8-6.7) and the median OS was 9.2 months (90% CI, 6.1-15.2). In addition, 11 patients remained on treatment (3-20 cycles).

Data on circulating tumor cells was available for 37 patients. The median number of circulating tumor cells prior to treatment with pembrolizumab was 1 (range, 0-256). Every unit gain in baseline circulating tumor cells was associated with poorer PFS (P = .052; adjusted for brain metastases, age and sex). PD-L1 expression was analyzed in 35 patients and was positive in one individual.

The most frequent adverse events included fatigue, nausea, cough and dyspnea.

“The adverse events observed with maintenance pembrolizumab are similar to what has been reported with this drug in other trials,” Gadgeel said. “One patient developed a complete heart block and subsequently passed away from the complications of this event, though that patient also had evidence of progression of disease, and one patient developed type 1 diabetes.”

While maintenance therapy with pembrolizumab did not improve median PFS in this patient population, “a subset of patients did appear to benefit,” and biomarkers are needed to identify the specific patients in whom pembrolizumab may be effective, according to Gadgeel.

“In an exploratory analysis, we found that patients whose tumors had PD-L1 expression at their stromal interface appeared to have a better outcome. However, this data needs to be viewed with a high level of caution, since the numbers are small and it’s unclear whether this is a predictor or a prognostic biomarker,” he said. “Ongoing pembrolizumab studies, including a study evaluating the addition of pembrolizumab to chemotherapy, will define the role of this drug in the management of patients with small cell lung cancer.” – by Julia Ernst, MS

Reference:

Gadgeel SM, et al. Abstract 8504. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosures: Gadgeel reports he is a consultant or advisor for ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech/Roche, Novartis and Pfizer; serves on the speakers bureau for AstraZeneca and Genentech/Roche; and receives research funding through his institution from ACEA Biosciences, Acerta Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb, Clovis Oncology, Five Prime Therapeutics, Genentech/Roche, Halozyme, Incyte, Janssen Oncology, Merck, Millennium, Novartis, OncoMed and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.

CHICAGO – Improvements in OS, but not PFS, indicate that maintenance treatment with pembrolizumab may benefit a subset of patients with small cell lung cancer, and biomarkers are needed to identify individuals in whom pembrolizumab may be effective, according to findings presented at the ASCO Annual Meeting.

“The standard of care for these patients – 4 to 6 cycles of platinum plus etoposide – has not changed in the United States in the last 30 years,” Shirish Gadgeel, MD, of the Karmanos Cancer Institute in Detroit, said during a presentation. “Despite a high response rate with this therapy, overall outcomes for these patients are quite poor. There is a need to identify other agents that can provide benefit in these patients.”

Gadgeel and colleagues enrolled patients with extensive-stage small cell lung cancer who had received 4 to 6 cycles of platinum plus etoposide and had either responded to therapy or had stable disease. Participants were required to start treatment with pembrolizumab within 8 weeks of finishing chemotherapy; restaging scans were conducted no more than 3 weeks before beginning pembrolizumab. Prophylactic cranial radiation was allowed.

Participants received 200 mg IV pembrolizumab every 3 weeks for a maximum duration of 2 years. The researchers performed disease assessments every 2 cycles throughout the first 6 cycles; future evaluations were guided by investigator choice.

The primary outcome of the study was PFS. PFS according to immune-related response criteria and OS were also evaluated.

The researchers examined tumor tissue for PD-L1 expression via the DAKO 22CE antibody and classified expression at any level as positive for PD-L1. Blood for circulating tumor cells was drawn before the first, second and third cycles of pembrolizumab.

Gadgeel and colleagues enrolled 45 patients. Slightly more than half (55%) were men and 22% had brain metastases. The median age of patients was 66 years.

Median time from completion of chemotherapy to initiation of pembrolizumab was 5 weeks. Patients were treated with a median of 4 cycles of pembrolizumab (range, 1-20). Most patients (n = 35) had measurable disease at the time of study entry.

The rate of disease control seen with pembrolizumab was 42%. One patient had a complete response; three achieved a partial response and 15 had stable disease.

Median PFS at the median follow-up point of 6 months was 1.4 months (90% CI, 1.3-4.0). The PFS according to immune-related response criteria was 4.7 months (90% CI, 1.8-6.7) and the median OS was 9.2 months (90% CI, 6.1-15.2). In addition, 11 patients remained on treatment (3-20 cycles).

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Data on circulating tumor cells was available for 37 patients. The median number of circulating tumor cells prior to treatment with pembrolizumab was 1 (range, 0-256). Every unit gain in baseline circulating tumor cells was associated with poorer PFS (P = .052; adjusted for brain metastases, age and sex). PD-L1 expression was analyzed in 35 patients and was positive in one individual.

The most frequent adverse events included fatigue, nausea, cough and dyspnea.

“The adverse events observed with maintenance pembrolizumab are similar to what has been reported with this drug in other trials,” Gadgeel said. “One patient developed a complete heart block and subsequently passed away from the complications of this event, though that patient also had evidence of progression of disease, and one patient developed type 1 diabetes.”

While maintenance therapy with pembrolizumab did not improve median PFS in this patient population, “a subset of patients did appear to benefit,” and biomarkers are needed to identify the specific patients in whom pembrolizumab may be effective, according to Gadgeel.

“In an exploratory analysis, we found that patients whose tumors had PD-L1 expression at their stromal interface appeared to have a better outcome. However, this data needs to be viewed with a high level of caution, since the numbers are small and it’s unclear whether this is a predictor or a prognostic biomarker,” he said. “Ongoing pembrolizumab studies, including a study evaluating the addition of pembrolizumab to chemotherapy, will define the role of this drug in the management of patients with small cell lung cancer.” – by Julia Ernst, MS

Reference:

Gadgeel SM, et al. Abstract 8504. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosures: Gadgeel reports he is a consultant or advisor for ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech/Roche, Novartis and Pfizer; serves on the speakers bureau for AstraZeneca and Genentech/Roche; and receives research funding through his institution from ACEA Biosciences, Acerta Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb, Clovis Oncology, Five Prime Therapeutics, Genentech/Roche, Halozyme, Incyte, Janssen Oncology, Merck, Millennium, Novartis, OncoMed and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.

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