6259 - Pembrolizumab With or Without Chemotherapy vs Chemotherapy in Patients With Advanced G/GEJ Cancer (GC) Including Outcomes According to Microsatellite Instability-High (MSI-H) Status in KEYNOTE-062

Background

KEYNOTE-062 (NCT02494583) was a randomized, study of 1L pembrolizumab (P) or pembro + chemo (P+C) vs chemo (C) in patients (pts) with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced GC.

Methods

Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m² + 5-FU 800 mg/m²/d on d1-d5 Q3W [or capecitabine 1000 mg/m² BID on d1-d14 Q3W per local guideline]) or placebo Q3W + C. Primary endpoints were OS in CPS ≥1 and CPS ≥10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS ≥1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS ≥1 for P+C vs C was the secondary endpoint. The final analysis cutoff date was 26 Mar 2019.

Results

763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS ≥1 per prespecified margins. P vs C prolonged OS in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. P+C vs C was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for P+C. In an exploratory analysis of pts with MSI-H tumors with CPS ≥1 (N = 50), median OS was not reached vs 8.5 mo for both P vs C (HR 0.29; 95% CI 0.11-0.81) and P+C vs C (HR 0.37; 95% CI 0.14-0.97). PFS was longer with P vs C (HR 0.72; 95% CI 0.31-1.68) and P+C vs C (HR 0.45; 95% CI 0.18-1.11). ORR was higher with P (57%) and P + C (65%) vs C (37%). Median DOR was 21.2 mo with P, not reached (P + C) vs 7.0 mo (C). Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C).Table:

LBA44

Conclusions

As 1L therapy for advanced GC, P was noninferior to C for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. P+C did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10. Clinical benefit was substantially enhanced in a small subset of pts with MSI-H tumors. The safety profile was more favorable for P vs C.

Clinical trial identification

NCT02494583.

Editorial acknowledgement

Medical writing assistance was provided by Luana Atherly-Henderson, an employee of Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

K. Shitara: Honoraria (institution): Novartis; Honoraria (institution): AbbVie; Honoraria (institution): Yakult; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: BMS; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical ; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Chugai Pharma. E. Van Cutsem: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Merck. Y. Bang: Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck Serano; Research grant / Funding (institution): Boehringer-Ingelheim; Advisory / Consultancy: Samyang Biopharma . C.S. Fuchs: Leadership role: CytomX Therapeutics; Advisory / Consultancy: Genentech; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Unum Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Taiho. L. Wyrwicz: Honoraria (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): BMS; Licensing / Royalties: Cervico. K.W. Lee: Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Green Cross Corp.; Research grant / Funding (institution): ASLAN Pharmaceuticals; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): LSK BioPharma; Research grant / Funding (institution): Merck KGaA; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Pfizer. M. Garrido: Advisory / Consultancy: MSD; Research grant / Funding (institution): Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Roche. H. Cheol Chung: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck-Serono; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (institution): Foundation medicine; Advisory / Consultancy: Taiho; Advisory / Consultancy: Celltrione; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Quintiles; Advisory / Consultancy: BMS; Research grant / Funding (institution): GSK; Research grant / Funding (institution): BMS-Ono; Research grant / Funding (institution): Taiho. H.R. Castro: Research grant / Funding (institution): Merck. W. Mansoor: Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Speaker Bureau / Expert testimony: BMS. M.I.F.M. Braghiroli: Honoraria (institution), Research grant / Funding (institution): Roche; Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Merck; Research grant / Funding (institution): AstraZeneca. E. Goekkurt: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD. J. Chao: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: FivePrime Therapeutics; Research grant / Funding (institution): Novonco Therapeutics. Z.A. Wainberg: Advisory / Consultancy: Aduro Bio; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: BMS; Advisory / Consultancy, Research grant / Funding (institution): Five Prime Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Sirtex Medical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Plexxikon. U. Kher: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc.. S. Shah: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc.. S..P. Kang: Shareholder / Stockholder / Stock options, Full / Part-time employment, Non-remunerated activity/ies, Patent: Merck & Co., Inc.. J. Tabernero: Advisory / Consultancy: Array Bio; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.