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Summary
VP1-2023: Pembrolizumab (pembro) plus chemotherapy (chemo) as first-line remedy for superior HER2-negative gastric or gastroesophageal junction (G/GEJ) most cancers: Part III KEYNOTE-859 examine
Printed: February 16, 2023
DOI: https://doi.org/10.1016/j.annonc.2023.01.006
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S.Y. Rha, L.S. Wyrwicz, P.E. Yanez Weber, … S. Bordia, P. Bhagia, D-Y. Oh
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Background
PD-1 inhibitors together with chemo have proven efficacy in G/GEJ most cancers. We current outcomes of the double-blind, placebo-controlled KEYNOTE-859 examine of pembro + fluoropyrimidine- and platinum-containing chemo for superior HER2-negative G/GEJ most cancers (NCT03675737).
Strategies
Sufferers (pts) with HER2-negative, domestically superior or metastatic G/GEJ adenocarcinoma of recognized PD-L1 mixed constructive rating (CPS) have been randomized 1:1 to pembro 200 mg or placebo IV Q3W for ≤35 cycles; all pts obtained investigator’s alternative of 5-FU + cisplatin (FP) or capecitabine + oxaliplatin (CAPOX). Randomization was stratified by area (Europe/Israel/North America/Australia vs Asia vs remainder of world), PD-L1 CPS (<1 vs ≥1), and chemo alternative (FP vs CAPOX). The first finish level was OS; secondary finish factors have been PFS, ORR, and DOR per RECIST v1.1 by blinded impartial central assessment and security. Efficacy was assessed within the ITT inhabitants, security within the as-treated inhabitants. Knowledge are from the interim evaluation (03 Oct 2022 information cutoff).
Outcomes
1579 pts have been randomized to pembro + chemo (n = 790) or placebo + chemo (n = 789). Median examine follow-up was 31.0 mo (vary 15.3-46.3). Baseline traits have been balanced between arms. Median OS was 12.9 mo with pembro + chemo vs 11.5 mo with placebo + chemo (HR 0.78, 95% CI 0.70-0.87; P < 0.0001). Median PFS was 6.9 mo vs 5.6 mo (HR 0.76, 95% CI 0.67-0.85; P < 0.0001). Outcomes have been usually constant throughout subgroups, together with these by PD-L1 CPS. ORR was 51.3% vs 42.0% (P = 0.00009). Median DOR was 8.0 mo vs 5.7 mo. Grade 3-5 treatment-related AEs occurred in 59.4% of 785 pts handled with pembro + chemo and 51.1% of 787 handled with placebo + chemo; 1.0% and a couple of.0%, respectively, died of treatment-related AEs.
Conclusions
Pembro + fluoropyrimidine- and platinum-containing chemo supplied statistically vital, clinically significant enhancements in OS, PFS, and ORR in pts with domestically superior or metastatic, HER2-negative G/GEJ adenocarcinoma of any PD-L1 expression stage. No new security alerts have been seen. These information help pembro + chemo as a brand new remedy possibility for this inhabitants.
Scientific trial identification
NCT03675737; initially posted 18 September 2018.