Gandhi L, et al. - Researchers performed a global, double-blind, placebo-controlled, phase 3 KEYNOTE-189 trial to compare the combination of pemetrexed and a platinum-based drug plus either pembrolizumab or placebo in patients with nonsquamous non–small-cell lung cancer (NSCLC) with any level of programmed death ligand 1 (PD-L1) expression. Findings suggested that 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 in patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations.

Methods

• Researchers performed random assignment (in a 2:1 ratio) of 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.
• Among the patients in the placebo-combination group who had verified disease progression, crossover to pembrolizumab monotherapy was permitted.
• Overall survival and progression-free survival, as assessed by blinded, independent central radiologic review were the primary end points.

Results

• 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 vs 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) after a median follow-up of 10.5 months.
• Researchers noted improvement in overall survival across all PD-L1 categories that were evaluated.
• The pembrolizumab-combination group demonstrated median progression-free survival of 8.8 months (95% CI, 7.6 to 9.2) compared to 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).
• In this study, adverse events of grade 3 or higher were encountered in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group.