Pembrolizumab plus Chemotherapy in Metastatic Non–Small‐Cell Lung Cancer
By L. Gandhi, D. Rodríguez-Abreu, S. Gadgeel, E. Esteban, E. Felip, F. De Angelis, M. Dómine, P. Clingan, M. Hochmair, S. Powell and 19 more. New England Journal of Medicine, 2018
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BACKGROUND First‐line therapy for advanced non–small‐cell lung cancer (NSCLC) that lacks targetable mutations is platinum‐based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD‐L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first‐line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression‐free survival than chemotherapy alone in a phase 2 trial. METHODS In this double‐blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum‐based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo‐combination group who had verified disease progression. The primary end points were overall survival and progression‐free survival, as assessed by blinded, independent central radiologic review. RESULTS After a median follow‐up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab‐combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebo‐combination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P<0.001). Improvement in overall survival was seen across all PD‐L1 categories that were evaluated. Median progression‐free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab‐combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo‐combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P<0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab‐combination group and in 65.8% of those in the placebo‐combination group. CONCLUSIONS In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum‐based drug resulted in significantly longer overall survival and progression‐free survival than chemotherapy alone. (Funded by Merck; KEYNOTE‐189 ClinicalTrials.gov number, NCT02578680.)
Subfields: Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/45c4bb785cf9aec9bc441bb825b6e069cde46730
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Citations in the corpus
- Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study (2020, result): “These findings are consistent with those of pembrolizumab plus chemotherapy in NSCLC.16,17 0 3 6 9 12 15 18 21 24 27 30 33 10 20 30 40 50 60 70 80 90 100 Time (months) On go in g Re po ns e (% ) 19.3% 3.3% 16.3% 1.3% 161 107 49 32 8 3 0 0 139 82 17 8 1 1 0 0 25 4 18 3 1 1 0 0 Pembrolizumab plus EP P”
- Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry (2019, background): “Immune checkpoint inhibitors (ICI) which block the Programmed Death-1 (PD-1) /Programmed Death Ligand 1 (PD-L1) axis are a new standard of care [4-6].”