Science and Research

Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer

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 .).
  • Gandhi, L.
  • Rodriguez-Abreu, D.
  • Gadgeel, S.
  • Esteban, E.
  • Felip, E.
  • De Angelis, F.
  • Domine, M.
  • Clingan, P.
  • Hochmair, M. J.
  • Powell, S. F.
  • Cheng, S. Y.
  • Bischoff, H. G.
  • Peled, N.
  • Grossi, F.
  • Jennens, R. R.
  • Reck, M.
  • Hui, R.
  • Garon, E. B.
  • Boyer, M.
  • Rubio-Viqueira, B.
  • Novello, S.
  • Kurata, T.
  • Gray, J. E.
  • Vida, J.
  • Wei, Z.
  • Yang, J.
  • Raftopoulos, H.
  • Pietanza, M. C.
  • Garassino, M. C.
  • Keynote- Investigators

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
  • Antineoplastic Agents, Immunological/adverse effects/*therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
  • Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality/secondary
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms/*drug therapy/genetics/mortality/pathology
  • Male
  • Middle Aged
Publication details
DOI: 10.1056/NEJMoa1801005
Journal: The New England journal of medicine
Pages: 2078-2092 
Number: 22
Work Type: Original
Location: ARCN
Disease Area: LC
Partner / Member: Ghd
Access-Number: 29658856
See publication on PubMed

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