Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper 2 – Gastrointestinal tumours, non-colorectal

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

Date

29 Sep 2019

Session

Proffered Paper 2 – Gastrointestinal tumours, non-colorectal

Presenters

Kohei Shitara

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

K. Shitara1, E. Van Cutsem2, Y. Bang3, C.S. Fuchs4, L. Wyrwicz5, K.W. Lee6, I. Kudaba7, M. Garrido8, H. Cheol Chung9, H.R. Castro10, W. Mansoor11, M.I.F.M. Braghiroli12, E. Goekkurt13, J. Chao14, Z.A. Wainberg15, U. Kher16, S. Shah16, S..P. Kang16, J. Tabernero17

Author affiliations

  • 1 Department Of Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2 Digestive Oncology, University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE
  • 3 Medical Oncology, Seoul National University Hospital, Seoul/KR
  • 4 Medical Oncology, Yale Cancer Center, 06520 - New Haven/US
  • 5 Medical Oncology, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej, Warsaw/PL
  • 6 Medical Oncology, Seoul National University Bundang Hospital, Seoul/KR
  • 7 Oncology, Latvian Oncology Center Rakus Gailezers, 1079 - Riga/LV
  • 8 Medical Oncology, Pontificia Universidad Catolica de Chile, 750-0000 - Santiago/CL
  • 9 Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 10 Oncology, Grupo Medico Angeles, 1015 - Guatemala/GT
  • 11 Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 12 Medical Oncology, ICESP - Instituto do Cancer do Estado de Sao Paulo, 01246-000 - Sao Paulo/BR
  • 13 Hope, Hematology Oncology Practice Eppendorf (Facharztzentrum Eppendor)f, 20249 - Hamburg/DE
  • 14 Department Of Medical Oncology And Therapeutics, City of Hope Comprehensive Cancer Center, 91010 - Duarte/US
  • 15 Oncology, Ronald Reagan UCLA Medical Center, 90095 - Los Angeles/US
  • 16 Oncology, Merck & Co., Inc., 07033 - Kenilworth/US
  • 17 Medical Oncology, Vall d’Hebron University Hospital. Vall d’Hebron Institute of Oncology VHIO., 08035 - Barcelona/ES
More

Resources

Abstract 6259

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

CPS ≥1P+CCPC
aMedian, mo (95% CI)N = 257N = 250N = 256N = 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)/ b99.2% CI0.85 (0.70-1.03)0.91 (0.74-1.10)
P = 0.0460.91b (0.69-1.18); NI margin = 1.2
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)
MSI-HN = 17/N=19N = 14/N=19
OSaNot reached (3.6-NR)/8.5 (5.3-20.8)Not reached (10.7-NR)/8.5 (5.3-20.8)
ORR, %64.7/36.857.1/36.8
PFSaNot reached (3.6-NR)/6.6 (4.4-8.3)11.2 (1.5-NR)/6.6 (4.4-8.3)
DOR, median, mo (range)NR (1.6+ to 34.5+)/7.0 (2.0-30.4+)21.2 (1.4+ to 33.6+)/7.0 (2.0-30.4+)

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings