ESMO 2016: First-Line Pembrolizumab Plus Chemotherapy Significantly Improves Outcomes in Advanced NSCLC
The addition of the programmed cell death protein 1 (PD-1) antibody pembrolizumab (Keytruda) to standard first-line chemotherapy for treatment-naive advanced non–small cell lung cancer significantly improves response rates and progression-free survival, Langer et al reported at the 2016 European Society for Medical Oncology (ESMO) Congress in Copenhagen (Abstract LBA46_PR).
“Pembrolizumab enables T cells to ‘reactivate’ and accomplish what they are designed to do—facilitate tumor cell killing,” said principal investigator Corey J. Langer, MD, Director of the Thoracic Oncology Program at the Abramson Cancer Center at the University of Pennsylvania.
KEYNOTE-021
In the phase II KEYNOTE-021 study, researchers randomized 123 patients with stage IIIB/IV, chemotherapy-naive, nonsquamous non–small cell lung cancer to receive four cycles of carboplatin and pemetrexed (Alimta, 500 mg/m2 every 3 weeks), with or without 24 months of treatment with pembrolizumab (200 mg every 3 weeks).
After a median follow-up of 10.6 months, researchers observed a significantly greater objective response rate (55% vs 29%, P = .0016) in patients who received pembrolizumab as well as chemotherapy, compared to those treated with chemotherapy alone. While patients were not selected by the amount of programmed cell death ligand 1 (PD-L1) expression in their tumor, researchers did note a higher response rate (~80%) for the pembrolizumab-chemotherapy combination in tumors with PD-L1 expression greater than or equal to 50%.
Participants in the pembrolizumab arm also experienced an improved progression-free survival (median = 13.0 months vs 8.9 months), although overall survival rates were similar between the two arms (6-month survival rate = 92%), in this early landmark assessment.
There was a higher incidence of adverse events of grade 3 severity or above in the pembrolizumab arm compared to the chemotherapy alone arm (39% vs 26%), but this had no impact on treatment discontinuation rates (10% for the pembrolizumab arm compared to 13% for the chemotherapy-only arm) or treatment-related deaths. The most common treatment-related adverse events were fatigue and nausea, which were more common in patients receiving pembrolizumab, and anemia, which was more common in the chemotherapy-alone arm of the study.
“This is the first randomized phase II trial in advanced, treatment-naive nonsquamous non–small cell lung cancer to assess the benefit of adding a monoclonal antibody targeting PD-1 to standard chemotherapy,” said Dr. Langer. “If these benefits are confirmed in an ongoing phase III trial, the results may radically alter the treatment paradigm in advanced non–small cell lung cancer.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
