Mini Oral session - Gastrointestinal tumours Mini Oral session

125O - Pembrolizumab + chemotherapy for advanced G/GEJ adenocarcinoma (GC): The phase III KEYNOTE-062 study

Presentation Number
125O
Lecture Time
02:35 PM - 02:40 PM
Session Name
Mini Oral session - Gastrointestinal tumours
Speakers
  • Hyun Cheol Chung
Location
Room 324, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
02:30 PM - 03:30 PM
Authors
  • Hyun Cheol Chung
  • Yung-Jue Bang
  • Josep Tabernero
  • Eric Van Cutsem
  • Charles S. Fuchs
  • Lucjan Wyrwicz
  • Keun-Wook Lee
  • Iveta Kudaba
  • Marcelo Garrido
  • Hugo Castro
  • Wasat Mansoor
  • Maria I. Braghiroli
  • Eray Goekkurt
  • Joseph Chao
  • Zev A. Wainberg
  • Uma Kher
  • Sukrut Shah
  • Kohei Shitara

Abstract

Background

KEYNOTE-062 (NCT02494583) was a randomized, active-controlled study of first-line (1L) pembrolizumab (pembro) or pembro+chemotherapy vs chemotherapy (chemo) in patients (pts) with PD-L1 combined positive score ≥1 (CPS ≥1), HER2–, advanced GC.

Methods

Eligible pts were randomly assigned 1:1:1 to pembro 200 mg Q3W, pembro+chemo (cisplatin 80 mg/m2 + 5-FU 800 mg/m2/d on d1-5 Q3W [or capecitabine 1000 mg/m2 BID on d1-14 Q3W per local guidelines]) or placebo+chemo Q3W for up to 2 y. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary end points were OS in CPS ≥1 and CPS ≥10 for pembro+chemo vs chemo and pembro vs chemo, and PFS (RECIST v1.1; central review) in CPS ≥1 for pembro+chemo vs chemo. Secondary end point was ORR (RECIST v1.1; central review) in CPS ≥1 for pembro+chemo vs chemo. Final analysis cutoff date was March 26, 2019.

Results

763 pts (281 with CPS ≥10 tumors) were randomly assigned to pembro+chemo (n = 257), pembro (n = 256), or chemo (n = 250). Median follow-up was 11.3 mo. Pembro was noninferior to chemo for OS in CPS ≥1 per prespecified margins. Pembro prolonged OS vs chemo in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but was not tested per analysis plan. Pembro+chemo was not superior to chemo for OS in CPS ≥1 or CPS ≥10; the trend for pembro+chemo was favorable. Pembro+chemo did not significantly prolong PFS in CPS ≥1. ORR was higher with pembro+chemo than with chemo. In pts with microsatellite instability–high tumors, median OS was not reached (pembro) vs 8.5 mo (chemo) (HR 0.29; 95% CI 0.11-0.81) and not reached (pembro+chemo) vs 8.5 mo (chemo) (HR 0.37; 95% CI 0.14-0.97). Grade 3-5 drug-related AE rates were 17% (pembro), 73% (pembro+chemo), and 69% (chemo).

Conclusions

As 1L therapy for advanced GC, pembro was noninferior to chemo for OS in CPS ≥1; improvement in OS was clinically meaningful in CPS ≥10. Pembro+chemo was not superior for OS and PFS in CPS ≥1 or OS in CPS ≥10. The safety profile was more favorable for pembro than for chemo.

125O

CPS ≥1Pembro + ChemoChemoPembro N = 256Chemo N = 250
N = 257N = 250
OSa12.5 (10.8-13.9)11.1 (9.2-12.8)10.6 (7.7-13.8)11.1 (9.2-12.8)
HR (95% CI)/99.2% CI0.85 (0.70-1.03)0.91 (0.74-1.10)/ 0.91 (0.69-1.18); NI margin = 1.2
P = 0.046
OS (MSI-H)an = 17n = 19 8.5 (5.3-20.8)n = 14n = 19 8.5 (5.3-20.8)
Not reached (3.6-NR)Not reached (10.7-NR)
PFSa6.9 (5.7-7.3)6.4 (5.7-7.0)2.0 (1.5-2.8)6.4 (5.7-7.0)
HR (95% CI)0.84 (0.70-1.02); P = 0.0391.66 (1.37-2.01)
CPS ≥10n = 99n = 90n = 92n = 90
OSa12.3 (9.5-14.8)10.8 (8.5-13.8)17.4 (9.1-23.1)10.8 (8.5-13.8)
HR (95% CI)0.85 (0.62-1.17); P = 0.1580.69 (0.49-0.97)
PFSa5.7 (5.5-8.2)6.1 (5.3-6.9)2.9 (1.6-5.4)6.1 (5.3-6.9)

Median, mo (95% CI).

Clinical trial identification

NCT02494583.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Traci Stuve, MA, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

H.C. Chung: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck-Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy: Celltrion; Advisory / Consultancy: Quintiles; Advisory / Consultancy: BMS; Research grant / Funding (institution): GSK; Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS-ONO. Y-J. Bang: 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): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; 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): Taiho; Advisory / Consultancy, Research grant / Funding (institution): Daiichi-Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy, Research grant / Funding (institution): GreenCross; Advisory / Consultancy: Samyang Biopharm; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Genexine; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): MacroGenics, Boston Biomedical, FivePrime, Curis, Taiho, Takeda, Ono, CKD Pharma. J. Tabernero: Advisory / Consultancy, Scientific consultancy role: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partn. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim. C.S. Fuchs: Advisory / Consultancy: Agios; Advisory / Consultancy: Bain Capital; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors, unexercised stock options: CytomX; Advisory / Consultancy: Dicerna; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Shareholder / Stockholder / Stock options, unexercised stock options: Entrinsic Health; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Genentech; Advisory / Consultancy: Gilead Sciences; Advisory / Consultancy: KEW; Advisory / Consultancy: Merck; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Taiho; Advisory / Consultancy: Unum. L. Wyrwicz: Research grant / Funding (institution): MSD; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): BMS; Non-remunerated activity/ies, Patent, royalties, other intellectual property: Cervico; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Halozyme; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Servier. 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: Research grant / Funding (institution): Novartis. W. Mansoor: Honoraria (self), Speaker Bureau / Expert testimony, Speaker\'s Bureau - ESMO 2018: Lilly. M.I. Braghiroli: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Merck. E. Goekkurt: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Servier. J. Chao: Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novonco Therapeutics; Advisory / Consultancy: Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: FivePrime Therapeutics. Z.A. Wainberg: Advisory / Consultancy: Sirtex Medical; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy, Research grant / Funding (institution): Five Prime Therapeutics; Advisory / Consultancy: Novartis; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Aduro Biotech; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Pfizer. 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. K. Shitara: Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Advisory / Consultancy: MSD; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): MediScience. All other authors have declared no conflicts of interest.

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