Pembrolizumab + Trastuzumab (PD-1/HER2) Sustains OS Gain in HER2+ G/GEJ Cancer

Pembrolizumab is a PD-1 inhibitor added to trastuzumab, an anti-HER2 antibody, plus platinum/fluoropyrimidine chemotherapy in the randomized Phase 3 KEYNOTE-811 first-line trial for untreated advanced/metastatic HER2-positive gastric/GEJ adenocarcinoma (n=698; NCT03615326). At 70.0 months median follow-up, OS improved to 20.0 vs 16.8 months in ITT (HR 0.81) and 20.1 vs 15.7 months in PD-L1 CPS≥1 tumors (HR 0.79), while PFS was 10.0 vs 8.1 months in ITT (HR 0.73) and 10.9 vs 7.3 months in CPS≥1 (HR 0.72); ORR was 72.6% vs 60.1% in ITT. Grade ≥3 TRAEs were higher with pembrolizumab (58.9% vs 51.2%) with no new safety signals, and the OS exceeds historical ToGA trastuzumab+chemo mOS of 13.8 months, though the incremental pembrolizumab gain remains modest.