Neoadjuvant and adjuvant pembrolizumab (pembro) + chemotherapy (chemo) for locally advanced gastric or gastroesophageal junction (G/GEJ) cancer: Patient-reported outcomes (PROs) from the phase III KEYNOTE-585 study

BackgroundIn the randomized, phase 3 KEYNOTE-585 study (NCT03221426), perioperative pembro + chemo vs placebo (pbo) + chemo significantly improved pCR (diff, 10.9%; 95% CI, 7.5-14.8; P<0.00001), with no new safety signals in patients (pts) with locally advanced G/GEJ cancer. Prespecified exploratory PROs are reported.MethodsEligible adults had untreated locally advanced resectable G/GEJ adenocarcinoma and ECOG PS of 0 or 1. Pts were randomly assigned 1:1 to receive neoadjuvant 200 mg pembro IV + chemo or pbo + chemo Q3W for 3 cycles, then surgery, adjuvant pembro + chemo or pbo + chemo Q3W for 3 cycles, then adjuvant pembro or pbo alone Q3W for 11 cycles. The main cohort had pembro or pbo + cisplatin-based doublet chemo; the safety cohort had pembro or pbo + FLOT. Health-related quality of life (HRQoL) was evaluated in pts who had ≥1 dose of treatment and ≥1 PRO assessment. PRO end points were least squares mean (LSM) change from baseline to week 6 (neoadjuvant) or week 39 (adjuvant) in subscales of EORTC QLQ-C30, EORTC QLQ-STO22, and EQ-5D-5L VAS. Week 6 was the only analysis time in the neoadjuvant phase; week 39 was the latest time in the adjuvant phase when completion was ≥60% and compliance was ≥80%. Improvement was a positive (EORTC QLQ-C30, EQ-5D-5L VAS) or negative (EORTC QLQ-STO22) LSM change. Database cutoff was Feb 16, 2024.ResultsThe PRO analysis comprised 980 pts (pembro + chemo, n=490; pbo + chemo, n=490). Median follow-up was 58.6 months (range, 36.7-75.8) for pembro + chemo and 58.5 (36.7-75.8) for pbo + chemo. LSM changes from baseline in the combined cohorts are in the table. Table: 1451P Change from baselinea in LSM (95% CI) to week 6 (neoadjuvant) or 39 (adjuvant) Neoadjuvant pembro + chemo Neoadjuvant pbo + chemo Adjuvant pembro + chemo Adjuvant pbo + chemo QLQ-C30 GHS/QoL n=489 n=488 n=374 n=371 –1.68 (–3.73 to 0.36) –4.73 (–6.79 to –2.68) 4.23 (1.99-6.47) 4.12 (1.94-6.31) QLQ-STO22 pain scale n=487 n=486 n=374 n=371 –3.14 (–4.95 to –1.34) –1.35 (–3.16 to 0.46) –5.30 (–7.45 to –3.15) –3.03 (–5.13 to –0.93) EQ-5D-5L VAS n=489 n=490 n=373 n = 371 –2.28 (–3.86 to –0.70) –3.08 (–4.67 to –1.49) 3.52 (1.86-5.18) 3.37 (1.75-5.00) aInitiation of therapy (neoadjuvant) or surgery (adjuvant). ConclusionsPembro + chemo did not worsen HRQoL vs pbo + chemo for pts with untreated locally advanced resectable G/GEJ cancer enrolled in KEYNOTE-585. Combined with the safety and efficacy results from KEYNOTE-585, HRQoL data support continued exploration of perioperative pembro combinations in these pts.Clinical trial identificationNCT03221426.Editorial acknowledgementMedical writing assistance was provided by Shane Walton, PhD, CMPP, and Holly C. Cappelli, PhD, CMPP, of ApotheCom (Yardley, PA, USA).Legal entity responsible for the studyMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.FundingMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.DisclosureK. Shitara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Takeda, Ono Pharmaceutical, MSD, Novartis, Daiichi Sankyo, Amgen, Guardant Health Japan Corp, Astellas Pharma Inc., Astellas, Bayer, AstraZeneca, Zymeworks Biopharmaceuticals Inc., ALX Oncology Inc.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Janssen, AstraZeneca, Eli Lilly, Astellas, Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Eisai, Amgen, PRA Health Sciences. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas, beringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, 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, Other, Drug 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: BeiGene; Financial Interests, Local PI: Roche. L.S. Wyrwicz: Financial Interests, Personal, Advisory Role: GSK, Servier; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel: Servier; Financial Interests, Personal, Other, Honoraria: BeiGene, Bristol Myers Squibb, MSD. T. Oshima: Financial Interests, Personal, Invited Speaker: Taiho, Astellas; Financial Interests, Personal, Writing Engagement: Astellas; Financial Interests, Personal, Other, research grant: Taiho, Kyowa Kirin, Chugai, Nihon Kayaku. M. Osipov: Non-Financial Interests, Personal, Principal Investigator: Leningrad Regional Clinical Hospital. 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, Takeda Pharmaceutical; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, Ono Pharmaceutical, Astellas Pharma, Amgen, AstraZeneca. S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, MSD Sharp & Dohme; Financial Interests, Personal, Invited Speaker: MCI Deutschland GmbH; Financial Interests, Personal, Ownership Interest, CEO: Institut für Klinische Krebsforschung IKF GmbH; Financial Interests, Institutional, Research Grant: Sanofi, Roche, Celgene, Lilly, Eurozyto, Immutep, Ipsen, Bristol Myers Squibb, MSD Sharp & Dohme, AstraZeneca, German Cancer Aid (Krebshilfe), German Research Foundation, Federal Ministry of Education and Research. M. Di Bartolomeo: Financial Interests, Institutional, Advisory Board: MSD, Lilly Spa, BMS; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Research Grant: Lilly Spa. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, Lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi Sankyo, Bristol Myers Squibb, Astellas, GSK, Takeda, Bayer, Rottapharm; Financial Interests, Personal, Invited Speaker: Pierre Fabre, GSK, Roche, Servier, Amgen, Bristol Myers Squibb, Incyte, Lilly, Merck Serono, MSD, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol Myers Squibb; Non-Financial Interests, Member of Board of Directors, Italian No-Profit Oncology Research Foundation supporting academic Clinical trials: GONO Foundation. Y. Guan: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A. Valderrama: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. C. Shih: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Proprietary Information: Merck & Co., Inc. X. Fang: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. Y. Bang: Financial Interests, Personal, Advisory Role: Astellas, Amgen, Hanmi, Daewong, SK Biopharm. All other authors have declared no conflicts of interest.