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Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: The phase 3 KEYNOTE-590 study

Date

21 Sep 2020

Session

Presidential Symposium III

Presenters

Ken Kato

Citation

Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325

Authors

K. Kato1, J. Sun2, M.A. Shah3, P.C. Enzinger4, A. Adenis5, T. Doi6, T. Kojima7, J. Metges8, Z. Li9, S. Kim10, B.C. Chul Cho11, W. Mansoor12, S. Li13, P. Sunpaweravong14, M.A. Maqueda15, E. Goekkurt16, Q. Liu17, S. Shah17, P. Bhagia17, L. Shen18

Author affiliations

  • 1 Gastrointestinal Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2 Medicine, Samsung Medical Center, Sungkyunkwan University, 135-710 - Seoul/KR
  • 3 Medical Oncology/solid Tumor Program, Weill Cornell Medical College, New York/US
  • 4 Medical Oncology, Dana Farber Cancer Institute, 02215 - Boston/US
  • 5 Medical Oncology, IRCM, Inserm, Université Montpellier, ICM, 34090 - Montpellier/FR
  • 6 Experimental Therapeutics, National Cancer Center Hospital East, 277-8577 - Chiba/JP
  • 7 Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 8 Cancer Institute, CHU Brest – Institut de Cancerologie et d’Hematologie, 29200 - Brest/FR
  • 9 Thoracic & Esophageal Surgery, Shanghai Chest Hospital, Esophageal Disease Center,, 200020 - Shanghai/CN
  • 10 Oncology, Asan Medical Center, Seoul/KR
  • 11 Yonsei Cancer Center, Severance Hospital, Yonsei University Health System, 3722 - Seoul/KR
  • 12 Medical Oncology, Christie Hospital NHS Trust, M20 4BX - Manchester/GB
  • 13 Oncology And Hematology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung/TW
  • 14 Medicine, Prince of Songkla University Hospital, 90110 - Songkhla/TH
  • 15 Medical Oncology, Vall d’Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 16 Hematology-oncology, Hematology Oncology Practice Eppendorf, and University Cancer Center Hamburg, 20249 - Hamburg/DE
  • 17 Medical Oncology, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., 07033 - Kenilworth/US
  • 18 Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, 100142 - Beijing/CN
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Abstract LBA8_PR

Background

KEYNOTE-590 (NCT03189719) is a randomized, international, double-blind study of 1L pembrolizumab (pembro) + chemotherapy (chemo) vs chemo alone in patients (pts) with locally advanced/unresectable or metastatic adenocarcinoma or esophageal squamous cell carcinoma (ESCC) or Siewert type 1 esophagogastric junction adenocarcinoma (EGJ).

Methods

Eligible pts were randomized 1:1 to pembro 200 mg or placebo Q3W for up to 2 yr + chemo (cisplatin 80 mg/m2 Q3W [d1; 6 doses] + 5-FU 800 mg/m2 on d1-5 Q3W). Randomization was stratified by Asia vs Rest of World, adenocarcinoma vs ESCC, and ECOG PS 0 vs 1. Treatment continued until progression, unacceptable toxicity, or withdrawal, or 2 yr. No crossover was permitted. Primary end points were OS in pts with ESCC PD-L1 combined positive score (CPS) ≥10 tumors, and OS and PFS (RECIST v1.1 ; by investigator) in ESCC, PD-L1 CPS ≥10, and all pts. The secondary end point was ORR (RECIST v1.1; by investigator) in all pts. Data cutoff for interim OS/final PFS analysis was July 2, 2020.

Results

At data cutoff, 749 pts (83% male, 73% ESCC) were randomized (373 pembro + chemo; 376 chemo). Median follow-up was 10.8 mo. Pembro + chemo vs chemo was superior for OS in pts with ESCC CPS ≥10 (median 13.9 vs 8.8 mo; HR 0.57; 95% CI, 0.43-0.75; P < 0.0001), ESCC (median 12.6 vs 9.8 mo; HR 0.72; 95% CI, 0.60-0.88; P = 0.0006), CPS ≥10 (median 13.5 vs 9.4 mo; HR 0.62; 95% CI, 0.49-0.78; P < 0.0001), and all pts (median 12.4 vs 9.8 mo; HR, 0.73, 95% CI, 0.62-0.86; P < 0.0001). PFS was superior with pembro + chemo vs chemo in ESCC (median 6.3 vs 5.8 mo; HR 0.65; 95% CI, 0.54-0.78; P < 0.0001), CPS ≥10 (median 7.5 vs 5.5 mo; HR 0.51; 95% CI, 0.41-0.65; P < 0.0001), and all pts (median 6.3 vs 5.8 mo; HR 0.65; 95% CI, 0.55-0.76; P < 0.0001). Confirmed ORR was 45.0% vs 29.3% (P < 0.0001) in all pts, with median DOR of 8.3 vs 6.0 mo. Grade 3-5 drug-related AE rates were 72% vs 68%. Discontinuation rates from drug-related AEs were 19% vs 12%.

Conclusions

Pembro + chemo provided superior OS, PFS, and ORR vs chemo, with a manageable safety profile in pts with untreated, advanced esophageal and EGJ cancer. These data demonstrate that 1L pembro + chemo is a new standard of care in this pt population.

Clinical trial identification

NCT03189719.

Editorial acknowledgement

Luana Atherly-Henderson of 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

K. Kato: Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): Beigene; Speaker Bureau/Expert testimony: Taiho; Speaker Bureau/Expert testimony: Eli Lilly; Research grant/Funding (institution): Shionogi; Research grant/Funding (institution): Merck Bio; Research grant/Funding (institution): Chugai. J-M. Sun: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Ono; Research grant/Funding (institution): MSD. M.A. Shah: Advisory/Consultancy: Daiichi; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Oncolys. P.C. Enzinger: Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy: Five-Prime; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Loxo; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme Corp.; Honoraria (self), Advisory/Consultancy: Taiho; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Zymeworks. A. Adenis: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self), Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Servier; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme Corp.; Research grant/Funding (institution): Pfizer. T. Doi: Honoraria (self), Research grant/Funding (institution): Bristol Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Abbvie; Honoraria (self): Astellas Pharma; Honoraria (self): Oncolys BioPharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self): Otsuka; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Sumitomo Dainippon; Advisory/Consultancy: Takeda; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy: Rakuten Medical; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): IQVIA. T. Kojima: Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self): Oncolys BioPharma; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy: Merck; Research grant/Funding (institution): Astellas Amgen BioPharma; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Shionogi. J-P. Metges: Honoraria (self): MSD; Honoraria (self): Bayer; Honoraria (self): Bristol Myers Squibb. S-B. Kim: Advisory/Consultancy, Research grant/Funding (self): Novartis; Research grant/Funding (self): Sanofi-Aventis; Research grant/Funding (self): DongKook Pharma Co.; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Advisory/Consultancy: Enzychem; Advisory/Consultancy: Dae Hwa Pharmaceutical Co. Ltd; Advisory/Consultancy: ISU Abxis; Advisory/Consultancy: Daiichi-Sankyo. B.C. Chul Cho: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): Yuhan; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Medpacto; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy, Shareholder/Stockholder/Stock options: KANAPH Therapeutic Inc.; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Brigebio Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Cyrus Therapeutics; Advisory/Consultancy: Guardant Health; Shareholder/Stockholder/Stock options: TheraCanVac Inc; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Gencurix Inc; Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Officer/Board of Directors: Interpark Bio Convergence Corp.; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): MOGAM Institute; Research grant/Funding (institution): Dong-A ST; Research grant/Funding (institution), Licensing/Royalties: Champions Oncology; Research grant/Funding (institution): Dizal Pharma; Advisory/Consultancy, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Abbvie; Research grant/Funding (institution): Medpacto; Research grant/Funding (institution): GIInnovation; Leadership role, founder: DAAN Biotherapeutics; Advisory/Consultancy: Takeda. S-H. Li: Research grant/Funding (institution): MSD. M.A. Maqueda: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Amgen. E. Goekkurt: Honoraria (self): MSD; Honoraria (self): Bristol Myers Squibb; Honoraria (self): Servier. Q. Liu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. S. Shah: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. P. Bhagia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. L. Shen: Advisory/Consultancy: Merck Sharp & Dohme Corp.; Advisory/Consultancy: Harbour; Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Beijing Xiantong Biomedical Technology; Research grant/Funding (self): Qilu Pharmaceutical; Research grant/Funding (self): Zaiding Pharmaceutical; Research grant/Funding (self): Jacobio Pharmaceuticals; Research grant/Funding (self): Beihai Kangcheng(Beijing)Medical Technology Co., Ltd. All other authors have declared no conflicts of interest.

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