Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Previously Untreated NSCLC: KEYNOTE-789 Extended Follow-Up
Background
The KEYNOTE-789 trial established pembrolizumab plus platinum-based chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (NSCLC). However, long-term efficacy and durability of responses beyond 3 years remained uncertain. We report the prespecified 5-year follow-up analysis of overall survival and progression-free survival.
Methods
This multicenter, double-blind, randomized phase 3 trial enrolled 1,278 patients with previously untreated metastatic non-squamous or squamous NSCLC without EGFR or ALK alterations. Patients were randomized 1:1 to receive pembrolizumab 200 mg plus platinum-based chemotherapy or placebo plus chemotherapy every 3 weeks for 4 cycles, followed by pembrolizumab or placebo maintenance for up to 35 cycles. The primary endpoints were overall survival and progression-free survival. This analysis includes data with a minimum follow-up of 60 months.
Results
At the 5-year analysis (median follow-up, 64.6 months), median overall survival was 22.0 months in the pembrolizumab-chemotherapy group versus 10.6 months in the chemotherapy-alone group (hazard ratio for death, 0.60; 95% CI, 0.52-0.69; P<0.001). The estimated 5-year overall survival rate was 19.4% versus 11.3%. Median progression-free survival was 9.0 versus 4.9 months (HR 0.49; 95% CI, 0.43-0.56). Among patients with PD-L1 tumor proportion score of 50% or higher, 5-year OS was 31.9%. Treatment-related adverse events of grade 3 or higher occurred in 67.2% of the pembrolizumab-chemotherapy group versus 65.8% in the chemotherapy group. Immune-mediated adverse events occurred in 27.8% of pembrolizumab-treated patients.
Conclusions
The addition of pembrolizumab to platinum-based chemotherapy provides significant and durable survival benefit in first-line treatment of metastatic NSCLC, with nearly one in five patients alive at 5 years. These data reinforce chemoimmunotherapy as the standard of care for this patient population.
Pembrolizumab combined with platinum-based chemotherapy significantly improves 5-year overall survival in previously untreated metastatic NSCLC, with durable responses observed regardless of PD-L1 expression level.