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1511O Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Survival results from the phase III, randomized, double-blind, placebo-controlled KEYNOTE-811 study

Annals of Oncology(2023)

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Abstract
In a previous analysis of the phase III KEYNOTE-811 study, pembrolizumab (pembro)/trastuzumab and chemotherapy (chemo) vs placebo (pbo)/trastuzumab and chemo provided an ORR of 74% vs 52% in the first 264 pts. These data led to FDA approval of first-line pembro/trastuzumab and chemo for HER2+ mG/GEJ adenocarcinoma. We present results of a prespecified interim analysis of PFS. Eligible patients (pts) aged ≥18 years with treatment-naive unresectable, HER2+ mG/GEJ adenocarcinoma irrespective of PD-L1 status were randomized 1:1 to pembro 200 mg IV Q3W or pbo IV Q3W plus chemo (5-FU and cisplatin [FP] or capecitabine and oxaliplatin [CAPOX] and trastuzumab [SOC]). Randomization was stratified by region, PD-L1 status, and chemo choice. Treatment continued for ≤2 years or until disease progression or intolerable toxicity. Dual primary end points were PFS (RECIST v1.1, BICR) or OS. Data cut-off for this interim analysis was May 25, 2022. Per the DSMC, OS assessment is ongoing. At data cut-off, 698 pts were randomized (350 to pembro + SOC; 348 to pbo + SOC). Median follow-up was 28.4 mo. In all pts, pembro + SOC vs pbo + SOC significantly improved PFS (median 10.0 vs 8.1 mo; HR 0.72; 95% CI 0.60-0.87; p=0.0002). In pts with PD-L1 CPS ≥1, median PFS was 10.8 vs 7.2 mo (HR 0.70; 95% CI, 0.58-0.85). 24-mo PFS rates were 27% vs 13%. At data cut-off, 75% of required OS events had occurred. OS follow-up is ongoing. ORR was 72.6% vs 59.8% with pembro + SOC vs pbo + SOC (73.2% vs 58.4% [PD-L1 CPS ≥1]); median (range) DOR was 11.2 mo (1.1+ to 40.1+) vs 9.0 mo (1.4+ to 38.3+). Approximately 31% vs 19% of responders had a response duration ≥24 mo. Grade ≥3 drug-related AE rates were 58% vs 51%. Grade 5 drug-related AEs occurred in 4 (1.1%) vs 3 (0.9%) pts, respectively. First-line pembro plus trastuzumab and chemo provided superior PFS, and improved ORR with durable responses vs pbo plus trastuzumab and chemo in pts with unresectable, HER2+ mG/GEJ adenocarcinoma, notably in pts with PD-L1 CPS ≥1. These efficacy and safety data continue to support use of this regimen in the first-line setting.
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Key words
metastatic gastric,adenocarcinoma,1511o pembrolizumab,trastuzumab,chemotherapy,double-blind,placebo-controlled
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