LBA74 - Pembrolizumab plus chemotherapy vs chemotherapy as neoadjuvant and adjuvant therapy in locally-advanced gastric and gastroesophageal junction cancer: The phase III KEYNOTE-585 study

Background

The phase 3 KEYNOTE-585 study (NCT03221426) evaluated neoadjuvant/adjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo in locally-advanced, resectable gastric or gastroesophageal junction (G/GEJ) cancer. A separate cohort evaluated pembro + FLOT. We report results of the pre-specified third interim analysis (IA3).

Methods

Patients (pts) with untreated, locally-advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W or pbo + chemo (cisplatin + capecitabine or cisplatin + 5-FU) for 3 cycles. After surgery, pts received adjuvant pembro or pbo + chemo Q3W for 3 cycles, then adjuvant pembro or pbo Q3W for 11 cycles (main cohort). In the FLOT cohort, pts were randomized 1:1 to pembro + docetaxel, oxaliplatin, leucovorin, and 5-FU, Q2W. Primary end points were pathCR rate (BICR), EFS (RECIST 1.1, by investigator), OS (main cohort), and safety (FLOT cohort).

Results

804 pts were randomized to the main (402 pembro; 402 pbo) and 1007 to main + FLOT ([502 pembro; 505 pbo) cohorts. Median follow-up was 47.7 mo and 46.3 mo, respectively. In the main cohort, pathCR significantly improved with pembro + chemo (12.9% [95% CI, 9.8-16.6]) vs pbo + chemo (2.0 [95% CI, 0.9-3.9]); Δ (10.9% [95% CI, 7.5-14.8]; P<0.00001). EFS was longer with pembro vs pbo (median 44.4 vs 25.3 mo; HR 0.81; 95% CI, 0.67-0.99; P=0.0198), but was not significant. OS continues to final analysis. Median OS was 60.7 vs 58.0 mo (HR 0.90; 95% CI, 0.73-1.12) at IA3. Grade ≥3 drug-related AE rates were 65% with pembro + chemo and 63% with pbo + chemo. Outcomes in the main + FLOT cohort are in the Table. Table: LBA74

Outcomes in main + FLOT cohort

^aIn first 987 pts randomized; HR, hazard ratio; NA, not applicable; NR, not reached

Conclusions

Neoadjuvant/adjuvant pembro + chemo followed by adjuvant pembro, significantly improved pathCR rate with no significant improvement in EFS vs placebo + chemo in pts with untreated, locally-advanced resectable G/GEJ cancer.

Clinical trial identification

NCT03221426.

Editorial acknowledgement

Medical writing assistance was provided by Luana Atherly-Henderson employed by the sponsor.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

K. Shitara: Financial Interests, Personal, Advisory Board: Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, AbbVie, GSK, Daiichi Sankyo, Amgen, Boehringer Ingelheim, Guardant Health Japan Corp, Astellas Pharma Inc.; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Eisai, Amgen; Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K.. 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, 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: zy,meworks; Financial Interests, Institutional, Local PI, drug supply for clinical trial: BeiGene; Financial Interests, Coordinating PI, Drug supply for clnical trial: Incyte. L.S. Wyrwicz: Financial Interests, Personal, Advisory Board: BMS, Servier; Financial Interests, Personal and Institutional, Local PI: BMS, MSD, Servier, BeiGene, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: AstraZeneca. 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. N. Karaseva: Financial Interests, Institutional, Funding: MSD. M. Osipov: Financial Interests, Institutional, Funding: MSD. 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. H. Yabusaki: Financial Interests, Institutional, Funding: MSD. S. Afanasyev: Financial Interests, Institutional, Research Funding: MSD. Y. Park: Financial Interests, Institutional, Funding: MSD. S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol-Myers Squibb, MacroGenics, Immutep, MSD Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, Lilly, AIO Studien gGmbH, MCI Deutschland GmbH; Financial Interests, Personal, Other, CEO/founder: Institute of Clinical Cancer Research IKF at Northwest Hospital; Financial Interests, Institutional, Research Grant: Sanofi, Roche, Celgene, Vifor, Medac, Hospira, Lilly, Eurozyto, Immutep, Ipsen, Bristol-Myers Squibb, MSD Sharp & Dohme, AstraZeneca, German Cancer Aid (Krebshilfe), German Research Foundation, Federal Ministry of Education and Research. T. Yoshikawa: Financial Interests, Personal, Other, honoraria: MSD, Ono, BMS, Daiichi Sankyo, Astra-Zeneca, TERUMO, Otsuka, Covidien, Johnson and Johnson, Olympus, Intuitive. P.E. Yanez Weber: Financial Interests, Institutional, Funding: MSD. M. Di Bartolomeo: Financial Interests, Personal, Other, honoraria: MSD, BMS, Novartis, Lilly, Servier; Financial Interests, Personal, Other, Travel: Daiichi; Financial Interests, Personal, Advisory Board: Novartis. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, merck serono, lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi Sankyo, Bristol-Myers Squibb, Astellas, GSK, Takeda, Bayer; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, GSK, Roche, Servier, Amgen, Bristol-Myers Squibb, Incyte, Lilly, Merck Serono, MSD; 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: GONOFoundation. X. Fang: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.. C. Shih: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. P. Bhagia: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. Y. Bang: Financial Interests, Personal, Advisory Role: Astellas, Amgen, Samyang Biopharm, Hanmi, Daewoong.