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NPJ Breast Cancer. 2024;10(1):79.

Results from the randomized KEYNOTE-355 study of pembrolizumab plus chemotherapy for Asian patients with advanced TNBC.

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제1저자 임석아 · 교신저자 임석아

PMID 39266535 PMC11393332 DOI 10.1038/s41523-024-00679-7 IF 8.4 혈액종양내과
소속 (22)
  1. Seoul National University Hospital, Seoul National University College of Medicine, Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. moisa@snu.ac.kr.
  2. International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Madrid and Barcelona, Spain.
  3. Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain.
  4. Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  5. Cancer Center at Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
  6. Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
  7. Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  8. The Cancer Institute Hospital of JFCR, Tokyo, Japan.
  9. Toranomon Hospital, Tokyo, Japan.
  10. National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  11. Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan.
  12. St. Marianna University Hospital, Kawasaki, Japan.
  13. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  14. Hyogo Cancer Center, Akashi, Hyogo, Japan.
  15. Saitama Cancer Center, Saitama, Japan.
  16. Division of Breast Surgery, The University of Hong Kong, Queen Mary and Tung Wah Hospital, Hong Kong, China.
  17. The University of Hong Kong-ShenZhen Hospital, Shenzhen, China.
  18. Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
  19. The Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Parkville, Australia.
  20. Merck & Co., Inc., Rahway, NJ, USA.
  21. University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA.
  22. Centre for Experimental Cancer Medicine, Barts Cancer Institute, London, UK.

Abstract

In the phase 3 KEYNOTE-355 study (NCT02819518), pembrolizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy among patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) and programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 10 tumors. We analyzed outcomes for the subgroup of patients enrolled in Asia in KEYNOTE-355. Patients received pembrolizumab 200 mg or placebo (2:1 randomization) every 3 weeks for 35 cycles plus investigator's choice chemotherapy. Primary endpoints were PFS per Response Evaluation Criteria in Solid Tumors version 1.1 and OS. Among patients enrolled in Hong Kong, Japan, Korea, Malaysia and Taiwan (pembrolizumab plus chemotherapy, n = 113; placebo plus chemotherapy, n = 47), 117 (73.1%) had PD-L1 CPS ≥ 1 and 56 (35.0%) had PD-L1 CPS ≥ 10. Median time from randomization to data cutoff (June 15, 2021) was 43.8 (range, 36.8‒53.2) months (intent-to-treat [ITT] population). Hazard ratios (HRs [95% CI]) for PFS in the CPS ≥ 10, CPS ≥ 1, and ITT populations were 0.48 (0.24‒0.98), 0.58 (0.37‒0.91), and 0.66 (0.44‒0.99), respectively. Corresponding HRs (95% CI) for OS were 0.54 (0.28‒1.04), 0.62 (0.40‒0.97), and 0.57 (0.39‒0.84). Grade 3/4 treatment-related adverse events (AEs) occurred in 77.9% versus 78.7% of patients with pembrolizumab plus chemotherapy versus placebo plus chemotherapy. No grade 5 AEs occurred. Clinically meaningful improvement in PFS and OS with manageable toxicity were observed with pembrolizumab plus chemotherapy versus placebo plus chemotherapy in patients enrolled in Asia with previously untreated, inoperable or metastatic TNBC.Trial registration: ClinicalTrials.gov, NCT02819518.

© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates & The Authors 2024.

Figures

Fig. 1
Fig. 1 Patient disposition. aIncludes all patients who received 35 administrations of pembrolizumab or placebo and discontinued from chemotherapy. AE adverse event, CPS combined positive score, CR complete response, ITT intention-to-treat, PD progressive disease, PD-L1 programmed cell death ligand 1.
Fig. 2
Fig. 2 Progression-free survival. Results in (A) patients with tumor PD-L1 CPS ≥ 10, (B) patients with tumor PD-L1 CPS ≥ 1, and (C) the ITT population. CPS combined positive score, HR hazard ratio, PD-L1 programmed cell death ligand 1, ITT intention-to-treat.
Fig. 3
Fig. 3 Overall survival. Results in (A) patients with tumor PD-L1 CPS ≥ 10, (B) patients with tumor PD-L1 CPS ≥ 1, and (C) the ITT population. CPS combined positive score, HR hazard ratio, PD-L1 programmed cell death ligand 1, ITT intention-to-treat.

그림 출처: PubMed Central 공개 논문 (PMC11393332)

Conflict of interest statement

Seock-Ah Im: reports advisory role for AstraZeneca, Daiichi-Sankyo, GSK, Hanmi, Idience, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Novartis, Pfizer, Bertis and Roche; and grants for AstraZeneca, Boryung Pharm, Daewoong Pharm, Daiichi-Sankyo, Eisai, Pfizer, and Roche. Javier Cortes: Consulting/Advisor: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MSD, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, and Expres2ion Biotechnologies. Honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MSD, Daiichi Sankyo, and AstraZeneca. Research funding to institution: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardanth Health, MSD, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London. Stock: MedSIR, Nektar Pharmaceuticals, and Leuko (relative). Travel, accommodation, expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, and MSD. Patents: Pharmaceutical Combinations of a Pi3k Inhibitor and a Microtubule Destabilizing Agent.Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde. WO 2014/199294 A. ISSUED; Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy.Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/ 0338368 A1. LICENSED. David W. Cescon: Consultancy/Advisory: AstraZeneca, Exact Sciences, Eisai, Gilead, GlaxoSmithKline, Inflex, Inivata/Neogenomics, Lilly, MSD, Novartis, Pfizer, Roche, and SAGA. Research support (to institution): AstraZeneca, GlaxoSmithKline, Inivata, Knight, Merck, Pfizer, and Roche. Member of a trial steering committee: AstraZeneca, Merck, and GlaxoSmithKline. Holds a patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene. Mastura Md Yusof: Received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Merck, MSD, Specialised Therapeutics, Zuellig Pharma, Novartis, Pfizer, Roche, Eisai, Celgene; has received grant funding (to institution) from Astellas, AstraZeneca, Arcus, Genentech, Mundi Pharma, Novartis, Pfizer, Roche. Hiroji Iwata: Honoraria - AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Kyowa Hakko Kirin; Lilly Japan; Novartis; Pfizer. Consulting or Advisory Role - AstraZeneca; Chugai Pharma; Daiichi Sankyo; Kyowa Hakko Kirin; Lilly Japan; Novartis; Pfizer. Research Funding - AstraZeneca, Bayer, Chugai Pharma, Daiichi Sankyo, Eisai, GlaxoSmithKline, Kyowa Hakko Kirin, Lilly Japan, MSD, Nihonkayaku, Novartis, and Pfizer (all to institution). Norikazu Masuda: Leadership - Japan Breast Cancer Research Group Association (JBCRG). Honoraria - AstraZeneca; Chugai Pharma; Eisai; Lilly Japan; Pfizer. Research Funding – AstraZeneca, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa-Kirin, MSD, Novartis, Pfizer, and Sanofi (all to institution). Toshimi Takano: Lecture fees from Daiichi-Sankyo, Chugai, Kyowa Kirin, Eisai, Pfizer, Eli Lilly, and Celltrion. Research funding from Daiichi-Sankyo, Chugai, Eisai, Ono, and MSD. Chiun-Sheng Huang: Research grants: Aston Sci, AstraZeneca, Daiichi Sankyo, EirGenix, Eli Lilly, Gilead, MSD, Novartis, OBI Pharma, Pfizer, Roche, and Seagen. Honoraria: AstraZeneca, Daiichi Sankyo, Eli Lilly, Novartis, Pfizer, and Roche. Advisory fees: AstraZeneca, Daiichi Sankyo, Eli Lilly, Novartis, Pfizer, and Roche. Chi-Feng Chung: Honoraria: Daiichi Sankyo, Roche, Lotus, EirGenix, AstraZeneca, and Novartis. Koichiro Tsugawa: Honoraria: Pfizer and Kyowa Hakko Kirin. Research funding (to institution): Daiichi Sankyo. Yeon Hee Park: Consultancy or advisory fees: AstraZeneca, Eisai, Eli Lilly Export S.A. Puerto Rico Branch, Novartis, Pfizer, and Roche. Research funding: AstraZeneca, Merck, Novartis, Pfizer, and Roche. Koji Matsumoto: Honoraria: Chugai, Kyowa Hakko Kirin, and MSD. Research funding (to institution): Daiichi Sankyo, Eisai, Gilead Sciences, Lilly Japan, and MSD. Kenichi Inoue: Research funding: AstraZeneca, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa-Kirin, MSD, Novartis, Pfizer, Taiho, Ono, Astellas, and Sanofi (all to institution). Ava Kwong: Honoraria (for giving educational lectures and attending conferences): AstraZeneca, Pfizer, and Stryker Roche. Grant funding (to institution for clinical trials and research): AstraZeneca, Pfizer, MSD (Asia) Limited, and Roche. Sherene Loi: research funding to her institution from Novartis, Bristol-Myers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, Astra Zeneca, and Seattle Genetics. She has acted as consultant (not compensated) to Seattle Genetics, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, Eli Lilly, Pfizer, Gilead Therapeutics, and Roche-Genentech. She has acted as consultant (paid to her institution) to Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, Astra Zeneca, Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly, and Bristol-Myers Squibb. Wei Fu: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Wilbur Pan: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Vassiliki Karantza: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Hope S. Rugo: Research support to institution: Astellas Pharma Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Gilead Sciences, Inc.; GlaxoSmithKline; Eli Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals Inc.; Taiho Oncology, Inc., and Veru Inc. Consultancy/advisory support: Puma, NAPO, Blueprint, and Scorpion Therapeutics. Peter Schmid: has been a consultant to/received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, and Celgene; has received grant funding (to institution) from Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, and Medivation.

그 밖의 정보
출판 형태
Journal Article
저널
NPJ breast cancer · ISSN 2374-4677
전자 출판
2024-09-12
데이터
ClinicalTrials.gov: NCT02819518
참고문헌
34편