Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial

Charles S. Fuchs; Mustafa Özgüroğlu; Yung Jue Bang; Maria Di Bartolomeo; Mario Mandala; Min Hee Ryu; Lorenzo Fornaro; Tomasz Olesinski; Christian Caglevic; Hyun C. Chung; Kei Muro; Eric Van Cutsem; Anneli Elme; Peter Thuss-Patience; Ian Chau; Atsushi Ohtsu; Pooja Bhagia; Anran Wang; Chie Schin Shih; Kohei Shitara

doi:10.1007/s10120-021-01227-z

Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial

Charles S. Fuchs, Mustafa Özgüroğlu, Yung Jue Bang, Maria Di Bartolomeo, Mario Mandala, Min Hee Ryu, Lorenzo Fornaro, Tomasz Olesinski, Christian Caglevic, Hyun C. Chung, Kei Muro, Eric Van Cutsem, Anneli Elme, Peter Thuss-Patience, Ian Chau, Atsushi Ohtsu, Pooja Bhagia, Anran Wang, Chie Schin Shih, Kohei Shitara

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

Background: In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019). Methods: Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models. Results: 366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%). Conclusion: In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel. Trial registration: ClinicalTrials.gov, NCT02370498.

Original language	English
Pages (from-to)	197-206
Number of pages	10
Journal	Gastric Cancer
Volume	25
Issue number	1
DOIs	https://doi.org/10.1007/s10120-021-01227-z
Publication status	Published - 2022 Jan

Bibliographical note

Funding Information:
Charles S. Fuchs reports board membership (director of board) for CytomX; consultancy for Agios, Amylin Pharmaceuticals, AstraZeneca, Bain Capital, CytomX Therapeutics, Daiichi-Sankyo, Eli Lilly, Entrinsic Health, Genentech, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho, and Unum Therapeutics; expert testimony for Amylin Therapeutics and Eli Lilly; unexercised stock options for CytomX and Entrinsic Health; and co-founder of EvolveImmune Therapeutics. Mustafa Özgüroğlu has nothing to disclose. Yung-Jue Bang reports consultancy for Astellas Pharma, AstraZeneca, Bayer, BeiGene, BMS, Daiichi-Sankyo, Eli Lilly, Genentech/Roche, Genexine, GreenCross, Hanmi, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Samyang Biopharm, and Taiho; and grants from Astellas Pharma, AstraZeneca, Bayer, BeiGene, Boehringer-Ingelheim, BMS, Boston Biomedical, CKD Pharma, Curis, Daiichi-Sankyo, Eli Lilly, FivePrime, Genentech/Roche, Genexine, GreenCross, GSK, Macrogenics, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Ono, Pfizer, Taiho, and Takeda. Maria Di Bartolomeo has nothing to disclose. Mario Mandala reports board membership for Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; and grants from BMS, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche. Min-Hee Ryu reports honoraria from and advisory boards for AstraZeneca, BMS, Daehwa Pharmaceutical, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Ono, and Taiho; payment for lectures from BMS, Daehwa Pharmaceutical, Lilly, and Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Lorenzo Fornaro reports board membership for Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; payment for lectures, including service on speakers bureaus, from Eli Lilly; and travel/accommodations/meeting expenses from Celgene. Tomasz Olesinski has nothing to disclose. Christian Caglevic reports consultancy for Andes Biotechnologies, Boehringer Ingelheim, BMS, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; payment for lectures, including service on speakers bureaus, from BMS, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; travel/accommodations/meeting expenses from Roche; and service as a clinical trial investigator for Astellas Pharma, AstraZeneca, BMS, GSK, Medivation, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche. Hyun C. Chung reports consultancy for Amgen, BeiGene, BMS, Celltrion, Gloria, Lilly, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho, Zymework; and grants from Amgen, BeiGene, BMS/Ono, GSK Incyte, Lilly, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Taiho. Kei Muro reports grants from Astellas Pharma, Amgen Biopharma, Daiichi Sankyo, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Parexel International, Ono, Pfizer, Sanofi, Solasia Pharma, and Taiho; and consulting fees or honoraria from Amgen, AstraZeneca, Bayer, BMS, Chugai, Eli Lilly, Ono Pharmaceutical, Sanofi, Taiho, and Takeda. Eric Van Cutsem reports consultancy for Array, Astellas Pharma, AstraZeneca, Bayer, Biocartis, BMS, Celgene, Daichi-Sankyo, GSK, Halozyme, Incyte, Ipsen, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck KGaA, Novartis, Pierre-Fabre, Roche, Servier, Sirtex, and Taiho; and grants from Amgen, Bayer, Boehringer-Ingelheim, BSM, Celgene, Ipsen, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck KGaA, Novartis, Roche, and Servier. Anneli Elme has nothing to disclose. Peter Thuss-Patience reports consulting fees or honoraria from AstraZeneca, BMS, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Pfizer, Roche, and Servier. Ian Chau reports advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Eli Lilly, Five Prime Therapeutics, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Oncologie International, Pierre Fabre, Roche; research funding from Eli Lilly, Janssen-Cilag, and Sanofi Oncology; and honorarium from Eli Lilly. Atsushi Ohtsu reports personal fees from BMS, Chugai, Ono, and Taiho. Pooja Bhagia is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Anran Wang is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Chie-Schin Shih is an employee and stockholder of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Kohei Shitara reports consultancy with AbbVie, Astellas Pharma, BMS, Eli Lilly, GSK, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical; grants from Astellas Pharma, Chugai Pharma, Dainippon Sumitomo Pharma, Daiichi Sanyko, Eli Lilly, Medi Science, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Ono Pharmaceutical, and Taiho Pharmaceutical; and honoraria (lecture fees) from AbbVie, Novartis, and Yakult.

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

Oncology
Gastroenterology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s10120-021-01227-z

Cite this

Fuchs, C. S., Özgüroğlu, M., Bang, Y. J., Di Bartolomeo, M., Mandala, M., Ryu, M. H., Fornaro, L., Olesinski, T., Caglevic, C., Chung, H. C., Muro, K., Van Cutsem, E., Elme, A., Thuss-Patience, P., Chau, I., Ohtsu, A., Bhagia, P., Wang, A., Shih, C. S., & Shitara, K. (2022). Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer, 25(1), 197-206. https://doi.org/10.1007/s10120-021-01227-z

@article{84798f9936a64a3e9c7b8fcf6c8b0b9a,

title = "Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial",

abstract = "Background: In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019). Methods: Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models. Results: 366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%). Conclusion: In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel. Trial registration: ClinicalTrials.gov, NCT02370498.",

author = "Fuchs, {Charles S.} and Mustafa {\"O}zg{\"u}roğlu and Bang, {Yung Jue} and {Di Bartolomeo}, Maria and Mario Mandala and Ryu, {Min Hee} and Lorenzo Fornaro and Tomasz Olesinski and Christian Caglevic and Chung, {Hyun C.} and Kei Muro and {Van Cutsem}, Eric and Anneli Elme and Peter Thuss-Patience and Ian Chau and Atsushi Ohtsu and Pooja Bhagia and Anran Wang and Shih, {Chie Schin} and Kohei Shitara",

note = "Funding Information: Charles S. Fuchs reports board membership (director of board) for CytomX; consultancy for Agios, Amylin Pharmaceuticals, AstraZeneca, Bain Capital, CytomX Therapeutics, Daiichi-Sankyo, Eli Lilly, Entrinsic Health, Genentech, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho, and Unum Therapeutics; expert testimony for Amylin Therapeutics and Eli Lilly; unexercised stock options for CytomX and Entrinsic Health; and co-founder of EvolveImmune Therapeutics. Mustafa {\"O}zg{\"u}roğlu has nothing to disclose. Yung-Jue Bang reports consultancy for Astellas Pharma, AstraZeneca, Bayer, BeiGene, BMS, Daiichi-Sankyo, Eli Lilly, Genentech/Roche, Genexine, GreenCross, Hanmi, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Samyang Biopharm, and Taiho; and grants from Astellas Pharma, AstraZeneca, Bayer, BeiGene, Boehringer-Ingelheim, BMS, Boston Biomedical, CKD Pharma, Curis, Daiichi-Sankyo, Eli Lilly, FivePrime, Genentech/Roche, Genexine, GreenCross, GSK, Macrogenics, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Ono, Pfizer, Taiho, and Takeda. Maria Di Bartolomeo has nothing to disclose. Mario Mandala reports board membership for Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; and grants from BMS, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche. Min-Hee Ryu reports honoraria from and advisory boards for AstraZeneca, BMS, Daehwa Pharmaceutical, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Ono, and Taiho; payment for lectures from BMS, Daehwa Pharmaceutical, Lilly, and Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Lorenzo Fornaro reports board membership for Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; payment for lectures, including service on speakers bureaus, from Eli Lilly; and travel/accommodations/meeting expenses from Celgene. Tomasz Olesinski has nothing to disclose. Christian Caglevic reports consultancy for Andes Biotechnologies, Boehringer Ingelheim, BMS, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; payment for lectures, including service on speakers bureaus, from BMS, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; travel/accommodations/meeting expenses from Roche; and service as a clinical trial investigator for Astellas Pharma, AstraZeneca, BMS, GSK, Medivation, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche. Hyun C. Chung reports consultancy for Amgen, BeiGene, BMS, Celltrion, Gloria, Lilly, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho, Zymework; and grants from Amgen, BeiGene, BMS/Ono, GSK Incyte, Lilly, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Taiho. Kei Muro reports grants from Astellas Pharma, Amgen Biopharma, Daiichi Sankyo, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Parexel International, Ono, Pfizer, Sanofi, Solasia Pharma, and Taiho; and consulting fees or honoraria from Amgen, AstraZeneca, Bayer, BMS, Chugai, Eli Lilly, Ono Pharmaceutical, Sanofi, Taiho, and Takeda. Eric Van Cutsem reports consultancy for Array, Astellas Pharma, AstraZeneca, Bayer, Biocartis, BMS, Celgene, Daichi-Sankyo, GSK, Halozyme, Incyte, Ipsen, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck KGaA, Novartis, Pierre-Fabre, Roche, Servier, Sirtex, and Taiho; and grants from Amgen, Bayer, Boehringer-Ingelheim, BSM, Celgene, Ipsen, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck KGaA, Novartis, Roche, and Servier. Anneli Elme has nothing to disclose. Peter Thuss-Patience reports consulting fees or honoraria from AstraZeneca, BMS, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Pfizer, Roche, and Servier. Ian Chau reports advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Eli Lilly, Five Prime Therapeutics, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Oncologie International, Pierre Fabre, Roche; research funding from Eli Lilly, Janssen-Cilag, and Sanofi Oncology; and honorarium from Eli Lilly. Atsushi Ohtsu reports personal fees from BMS, Chugai, Ono, and Taiho. Pooja Bhagia is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Anran Wang is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Chie-Schin Shih is an employee and stockholder of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Kohei Shitara reports consultancy with AbbVie, Astellas Pharma, BMS, Eli Lilly, GSK, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical; grants from Astellas Pharma, Chugai Pharma, Dainippon Sumitomo Pharma, Daiichi Sanyko, Eli Lilly, Medi Science, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Ono Pharmaceutical, and Taiho Pharmaceutical; and honoraria (lecture fees) from AbbVie, Novartis, and Yakult. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = jan,

doi = "10.1007/s10120-021-01227-z",

language = "English",

volume = "25",

pages = "197--206",

journal = "Gastric Cancer",

issn = "1436-3291",

publisher = "Springer Japan",

number = "1",

}

Fuchs, CS, Özgüroğlu, M, Bang, YJ, Di Bartolomeo, M, Mandala, M, Ryu, MH, Fornaro, L, Olesinski, T, Caglevic, C, Chung, HC, Muro, K, Van Cutsem, E, Elme, A, Thuss-Patience, P, Chau, I, Ohtsu, A, Bhagia, P, Wang, A, Shih, CS & Shitara, K 2022, 'Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial', Gastric Cancer, vol. 25, no. 1, pp. 197-206. https://doi.org/10.1007/s10120-021-01227-z

Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer : 2-year update of the randomized phase 3 KEYNOTE-061 trial. / Fuchs, Charles S.; Özgüroğlu, Mustafa; Bang, Yung Jue et al.

In: Gastric Cancer, Vol. 25, No. 1, 01.2022, p. 197-206.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer

T2 - 2-year update of the randomized phase 3 KEYNOTE-061 trial

AU - Fuchs, Charles S.

AU - Özgüroğlu, Mustafa

AU - Bang, Yung Jue

AU - Di Bartolomeo, Maria

AU - Mandala, Mario

AU - Ryu, Min Hee

AU - Fornaro, Lorenzo

AU - Olesinski, Tomasz

AU - Caglevic, Christian

AU - Chung, Hyun C.

AU - Muro, Kei

AU - Van Cutsem, Eric

AU - Elme, Anneli

AU - Thuss-Patience, Peter

AU - Chau, Ian

AU - Ohtsu, Atsushi

AU - Bhagia, Pooja

AU - Wang, Anran

AU - Shih, Chie Schin

AU - Shitara, Kohei

N1 - Funding Information: Charles S. Fuchs reports board membership (director of board) for CytomX; consultancy for Agios, Amylin Pharmaceuticals, AstraZeneca, Bain Capital, CytomX Therapeutics, Daiichi-Sankyo, Eli Lilly, Entrinsic Health, Genentech, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho, and Unum Therapeutics; expert testimony for Amylin Therapeutics and Eli Lilly; unexercised stock options for CytomX and Entrinsic Health; and co-founder of EvolveImmune Therapeutics. Mustafa Özgüroğlu has nothing to disclose. Yung-Jue Bang reports consultancy for Astellas Pharma, AstraZeneca, Bayer, BeiGene, BMS, Daiichi-Sankyo, Eli Lilly, Genentech/Roche, Genexine, GreenCross, Hanmi, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Samyang Biopharm, and Taiho; and grants from Astellas Pharma, AstraZeneca, Bayer, BeiGene, Boehringer-Ingelheim, BMS, Boston Biomedical, CKD Pharma, Curis, Daiichi-Sankyo, Eli Lilly, FivePrime, Genentech/Roche, Genexine, GreenCross, GSK, Macrogenics, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Ono, Pfizer, Taiho, and Takeda. Maria Di Bartolomeo has nothing to disclose. Mario Mandala reports board membership for Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; and grants from BMS, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche. Min-Hee Ryu reports honoraria from and advisory boards for AstraZeneca, BMS, Daehwa Pharmaceutical, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Ono, and Taiho; payment for lectures from BMS, Daehwa Pharmaceutical, Lilly, and Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Lorenzo Fornaro reports board membership for Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; payment for lectures, including service on speakers bureaus, from Eli Lilly; and travel/accommodations/meeting expenses from Celgene. Tomasz Olesinski has nothing to disclose. Christian Caglevic reports consultancy for Andes Biotechnologies, Boehringer Ingelheim, BMS, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; payment for lectures, including service on speakers bureaus, from BMS, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche; travel/accommodations/meeting expenses from Roche; and service as a clinical trial investigator for Astellas Pharma, AstraZeneca, BMS, GSK, Medivation, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche. Hyun C. Chung reports consultancy for Amgen, BeiGene, BMS, Celltrion, Gloria, Lilly, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho, Zymework; and grants from Amgen, BeiGene, BMS/Ono, GSK Incyte, Lilly, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Taiho. Kei Muro reports grants from Astellas Pharma, Amgen Biopharma, Daiichi Sankyo, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Parexel International, Ono, Pfizer, Sanofi, Solasia Pharma, and Taiho; and consulting fees or honoraria from Amgen, AstraZeneca, Bayer, BMS, Chugai, Eli Lilly, Ono Pharmaceutical, Sanofi, Taiho, and Takeda. Eric Van Cutsem reports consultancy for Array, Astellas Pharma, AstraZeneca, Bayer, Biocartis, BMS, Celgene, Daichi-Sankyo, GSK, Halozyme, Incyte, Ipsen, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck KGaA, Novartis, Pierre-Fabre, Roche, Servier, Sirtex, and Taiho; and grants from Amgen, Bayer, Boehringer-Ingelheim, BSM, Celgene, Ipsen, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck KGaA, Novartis, Roche, and Servier. Anneli Elme has nothing to disclose. Peter Thuss-Patience reports consulting fees or honoraria from AstraZeneca, BMS, Lilly, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Pfizer, Roche, and Servier. Ian Chau reports advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Eli Lilly, Five Prime Therapeutics, Merck-Serono, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Oncologie International, Pierre Fabre, Roche; research funding from Eli Lilly, Janssen-Cilag, and Sanofi Oncology; and honorarium from Eli Lilly. Atsushi Ohtsu reports personal fees from BMS, Chugai, Ono, and Taiho. Pooja Bhagia is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Anran Wang is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Chie-Schin Shih is an employee and stockholder of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Kohei Shitara reports consultancy with AbbVie, Astellas Pharma, BMS, Eli Lilly, GSK, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical; grants from Astellas Pharma, Chugai Pharma, Dainippon Sumitomo Pharma, Daiichi Sanyko, Eli Lilly, Medi Science, Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Ono Pharmaceutical, and Taiho Pharmaceutical; and honoraria (lecture fees) from AbbVie, Novartis, and Yakult. Publisher Copyright: © 2021, The Author(s).

PY - 2022/1

Y1 - 2022/1

N2 - Background: In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019). Methods: Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models. Results: 366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%). Conclusion: In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel. Trial registration: ClinicalTrials.gov, NCT02370498.

AB - Background: In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019). Methods: Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models. Results: 366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%). Conclusion: In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel. Trial registration: ClinicalTrials.gov, NCT02370498.

UR - http://www.scopus.com/inward/record.url?scp=85114044149&partnerID=8YFLogxK

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U2 - 10.1007/s10120-021-01227-z

DO - 10.1007/s10120-021-01227-z

M3 - Article

C2 - 34468869

AN - SCOPUS:85114044149

SN - 1436-3291

VL - 25

SP - 197

EP - 206

JO - Gastric Cancer

JF - Gastric Cancer

IS - 1

ER -

Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial

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