FDA Approves Pembrolizumab as First-Line Combination Therapy With Pemetrexed and Carboplatin for Metastatic Nonsquamous NSCLC

On May 10, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda), an anti–programmed cell death protein 1 (PD-1) therapy, in combination with pemetrexed (Alimta) and carboplatin for the first-line treatment of metastatic nonsquamous non–small cell lung cancer (NSCLC), irrespective of programmed death-ligand 1 (PD-L1) expression. Under the FDA’s accelerated approval regulations, this indication is approved based on tumor response rate and progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.


The approval was based on data from the KEYNOTE-021 trial, Cohort G1, in 123 previously untreated patients with metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations and irrespective of PD-L1 expression. In this trial, pembrolizumab plus pemetrexed/carboplatin demonstrated an objective response rate (ORR) that was nearly double the ORR of pemetrexed/carboplatin alone: 55% (95% confidence interval [CI] = 42–68) compared to 29% (95% CI = 18–41), respectively; all responses were partial responses. Among patients who received pembrolizumab plus pemetrexed/carboplatin, 93% had a duration of response of 6 months or more (range = 1.4+ to 13.0+ months) compared to 81% who received pemetrexed/carboplatin alone (range = 1.4+ to 15.2+ months). In addition, findings demonstrated an improvement in PFS (hazard ratio [HR] = 0.53; 95% CI = 0.31–0.91, P = .0205), with a median PFS of 13.0 months (95% CI = 8.3–not estimable) for patients treated with pembrolizumab plus pemetrexed/carboplatin compared to 8.9 months (95% CI = 4.4–10.3) with pemetrexed/carboplatin alone.

Immune-mediated adverse reactions occurred with pembrolizumab including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Pembrolizumab can also cause severe or life-threatening infusion-related reactions.

“The improved responses seen with the pembrolzimab plus pemetrexed/carboplatin regimen are significant, and highlight the importance of finding new approaches that address the unmet needs of patients with metastatic nonsquamous non–small cell lung cancer,” said Roger M. Perlmutter, MD, PhD, President, Merck Research Laboratories.

“This approval marks an important milestone in the treatment of lung cancer. Now, pembrolizumab in combination with pemetrexed and carboplatin can be prescribed in the first-line setting for patients with metastatic nonsquamous non–small cell lung cancer, irrespective of PD-L1 expression,” said Corey Langer, MD, Director of Thoracic Oncology and Professor of Medicine at the Hospital of the University of Pennsylvania. “Physicians should continue to use each patient’s individual characteristics—including biomarker status, histology, and other clinical factors—to determine the best treatment plan for each person.”

The combination therapy indication makes pembrolizumab an option for more patients. Pembrolizumab is the only anti–PD-1 approved in the first-line setting as both monotherapy and combination therapy for appropriate patients with metastatic NSCLC. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.

“The combination of this immunotherapy with pemetrexed and carboplatin is more good news for patients,” said Bonnie J. Addario, a lung cancer survivor and Founder of the Bonnie J. Addario Lung Cancer Foundation. “Congratulations to Merck and the FDA for moving so swiftly on this important addition to our patients’ options for treatment. With this approval, hope for lung cancer patients continues to improve.”

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®.