Pembrolizumab (PD-1) + platinum doublet chemo shows larger OS benefit after crossover adjustment in 1L metastatic NSCLC

Pembrolizumab is an anti–PD-1 monoclonal antibody; here, pooled 5-year follow-up datasets from Phase 3 KEYNOTE-189 (nonsquamous; n=646 across global + Japan extension) and KEYNOTE-407 (squamous; n=669 across global + China extension) re-estimated overall survival (OS) after accounting for heavy control-arm immunotherapy exposure (chemo-arm crossover/subsequent anti–PD-(L)1: 56.3% in KN-189; 53.7% in KN-407). In ITT, OS HRs for pembrolizumab+chemo vs chemo were 0.60 (0.50–0.72) in KN-189 and 0.65 (0.55–0.76) in KN-407, but after adjustment the estimated treatment effect strengthened: KN-189 HR 0.44 (0.33–0.58) via two-stage estimation (TSE) and 0.46 (0.35–0.61) via RPSFT; KN-407 HR 0.47 (0.35–0.63) via TSE and 0.52 (0.40–0.67) via RPSFT, with consistent direction across PD-L1 TPS subgroups (including TPS <1%). No new safety results were reported in this crossover-adjustment analysis; in practice, these adjusted HRs are best interpreted as “what OS might have looked like” if the control arm had not accessed PD-(L)1 therapy—i.e., a hypothetical effect size, not a new randomized comparison.