138MO - Pembrolizumab (Pembro) or placebo (Pbo) plus chemotherapy (Chemo) for advanced HER2-negative gastric/gastroesophageal junction (G/GEJ) adenocarcinoma (KEYNOTE-859): Asia subgroup analysis

Background

In the global, double-blind, placebo-controlled, phase 3 KEYNOTE-859 study (NCT03675737) of pembro + fluoropyrimidine- and platinum-containing chemo for patients (pts) with advanced HER2-negative G/GEJ adenocarcinoma, OS, PFS, and ORR were significantly improved with manageable safety, regardless of PD-L1 expression. Results for the subgroup of pts enrolled in Asia are reported.

Methods

Pts with previously untreated HER2-negative locally advanced or metastatic G/GEJ adenocarcinoma with known PD-L1 CPS were randomized 1:1 to pembro 200 mg (pembro arm) or pbo (pbo arm) every 3 weeks for ≤35 cycles; all pts received investigator’s choice of 5-FU + cisplatin (FP) or capecitabine + oxaliplatin (CAPOX). The primary end point was OS; key secondary end points were PFS and ORR per RECIST v1.1 by blinded independent central review and safety. Data are from the interim analysis (3 Oct 2022 data cutoff).

Results

The Asia subgroup included 263 pts in the pembro arm and 262 pts in the pbo arm. The median (range) follow-up (defined from randomization to database cutoff date) was 28.6 (15.3-46.2) mo. Baseline characteristics were generally well balanced between treatment arms. Median OS was 17.3 mo (95% CI, 14.8-19.5) for the pembro arm vs 13.0 mo (11.8-14.4) for the pbo arm (HR, 0.71; 95% CI, 0.58-0.87); median PFS was 8.4 mo (95% CI, 7.2-9.6) for the pembro arm vs 6.7 mo (5.7-6.9) for the pbo arm (HR, 0.69; 0.57-0.85). ORR was 61.2% in the pembro arm and 48.9% in the pbo arm, estimated difference, 12.4% (95% CI, 3.9-20.7). Grade 3-5 treatment-related AEs occurred in 59.5% of pts in the pembro arm and 44.7% of pts in the pbo arm (grade 5: 1 [0.4%] vs 2 pts [0.8%]). Immune-mediated AEs and infusion reactions occurred in 83 pts (31.7%) and 34 pts (13.0%) in the pembro and pbo arms, respectively.

Conclusions

Consistent with the global KEYNOTE-859 results, the addition of pembro to FP or CAPOX provided improvement in OS, PFS, and ORR numerically, with no new safety signals for pts enrolled in Asia. Results continue to support pembro + chemo as a 1L treatment option for pts with locally advanced or metastatic HER2-negative G/GEJ adenocarcinoma.

Clinical trial identification

NCT03675737.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Andrea Humphries, PhD, CMPP, of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

Y. Bai: Financial Interests, Personal, Funding: Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca, MSD, Eli Lily, Taiho Pharmaceutical, Novartis, Daehwa, Daiichi Sankyo, Astellas. M.H. Ryu: Financial Interests, Personal, Funding: Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca, MSD, Eli Lily, Taiho Pharmaceutical, Novartis, Daehwa, Daiichi Sankyo, Astellas. H. Yasui: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Chugai Pharma, Bristol Myers Squibb, Daiichi Sankyo, Terumo, Eli Lilly Japan, Merck Biopharma, Yakult Honsha, Bayer Yakuhin; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, Ono Pharmaceutical, Astellas Pharma, Amgen. K. Yamaguchi: Financial Interests, Personal, Invited Speaker: Taiho Pharm; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Bristol Mayers Squibbb, Ono Pharm, Eli Lilly Japan; Financial Interests, Institutional, Funding: Taiho Pharm. K. Yeh: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, PhytoHealth, Novartis, Ono, Merck, AstraZeneca; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, American Association for Cancer Research. L. Yin, S. Bordia, P. Bhagia: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Personal, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clincal trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: Zymeworks; Financial Interests, Institutional, Local PI, drug supply for clincial trial: Beigine; Financial Interests, Personal, Coordinating PI, Drug supply for clnical trial: Incyte. All other authors have declared no conflicts of interest.