Health-related quality of life in participants with advanced biliary tract cancer from the randomized phase III KEYNOTE-966 study
- PMID: 40154623
- DOI: 10.1016/j.jhep.2025.03.019
Health-related quality of life in participants with advanced biliary tract cancer from the randomized phase III KEYNOTE-966 study
Abstract
Background & aims: In the randomized, double-blind, phase III KEYNOTE-966 trial, the addition of pembrolizumab to gemcitabine and cisplatin (GemCis) led to a significant improvement in overall survival vs. GemCis alone for the first-line treatment of advanced biliary tract cancer (BTC). Herein, we present the prespecified health-related quality of life (HRQoL) outcomes from KEYNOTE-966.
Methods: HRQoL was assessed using the EORTC Core Quality of Life Questionnaire (QLQ-C30), EORTC QLQ-BIL21, and EQ-5D-5L questionnaires. Data from the latest time point with ≥60% completion and ≥80% compliance (week 18) were compared to baseline. Least squares means for change from baseline to week 18 were compared using a constrained longitudinal analysis model in six prespecified domains: QLQ-C30 global health status/quality of life, physical functioning, and role functioning; QLQ-BIL21 pain and jaundice scores, and EQ-5D-5L visual analogue score. The analysis population was all treated participants with ≥1 completed HRQoL assessment. Between-arm difference in time to confirmed deterioration was assessed using a stratified Cox proportional hazards model with randomization stratification factors.
Results: In KEYNOTE-966, 1,069 participants were randomized (533 to the GemCis+pembrolizumab arm and 536 to the GemCis+placebo arm). Questionnaire compliance was >87% from baseline to week 18 in both arms. Least squares means changes from baseline to week 18 were similar between arms for all prespecified domains. Time to confirmed deterioration estimates were also similar between arms, including for global health status/quality of life (median not reached [NR] in the pembrolizumab arm vs. 21.2 months in the placebo arm; hazard ratio [HR] 0.86, 95% CI 0.70-1.07); jaundice (NR vs. NR; HR 1.20, 95% CI 0.94-1.54), and pain (NR vs. NR; HR 0.79, 95% CI 0.59-1.05).
Conclusion: HRQoL was maintained after adding pembrolizumab to GemCis, further supporting this regimen as a first-line treatment option for advanced BTC.
Impact and implications: Biliary tract cancer (BTC) is often diagnosed at late stages because most patients do not present with disease-specific symptoms. Compared with the general population, patients with advanced BTC report worse physical, emotional, and functional well-being. In KEYNOTE-966, adding the PD-1 (programmed cell death protein 1) inhibitor pembrolizumab to gemcitabine and cisplatin as first-line therapy for participants with advanced BTC produced a statistically significant and clinically meaningful improvement in overall survival. The prespecified patient-reported outcome results from KEYNOTE-966 presented herein demonstrated that health-related quality of life was maintained after adding pembrolizumab to gemcitabine and cisplatin, further supporting this regimen as a first-line treatment option for advanced BTC.
Clinical trial registration: NCT04924062.
Keywords: biliary tract neoplasms; cisplatin; gemcitabine; immune checkpoint inhibitors; patient reported outcome measures; pembrolizumab; quality of life.
Copyright © 2025 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Conflict of interest The study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD). CY, MU, H-JK, RKK, AV, JF, ZR, TY, SLC, MO, SCO, SH, JOP, JWV, JE, JGK, SK, JMN, LY, UM, and RSF report funding to their institution from MSD to support the conduct of this study. All authors received medical writing and editorial support for the preparation of this manuscript from MSD. CY additionally reports honoraria from AstraZeneca, Bayer, Boryung Pharmaceuticals, Bristol Myers Squibb, Celgene, Eisai, Ipsen, MSD Oncology, Novartis, and SERVIER; and research funding from AstraZeneca, Bayer, and SERVIER. MU additionally reports honoraria from AstraZeneca, Chugai Pharma, Daiichi Sankyo/UCB Japan, Incyte, MSD, Mylan, Novartis, Ono Pharmaceutical, SERVIER, Taiho Pharmaceutical, Takeda, and Yakult Honsha; consulting or advisory fees from Boehringer Ingelheim and Novocure; and research funding to their institution from Astellas Pharma, AstraZeneca, Chiome Bioscience, Chugai Pharma, Delta-Fly Pharma, Eisai, Incyte, JPH Clinical Development, MSD, Novartis, Ono Pharmaceutical, and Taiho Pharmaceutical. H-JK additionally reports consulting fees to their institution from AstraZeneca and Janssen Oncology; and speakers' bureau fees to their institution from IPSEN and Medtalks. RKK additionally reports consulting fees to their institution from Agios, AstraZeneca, Exelixis/Ipsen, and Merck; consulting fees to themselves from Compass Therapeutics, Elevar, Jazz, Kinnate Biopharma, Moderna, Regeneron, and Tyra Biosciences; research funding to their institution from Adaptimmune, Agios, AstraZeneca, Bayer, Bristol Myers Squibb, EMD Serono, Exelixis, Genentech/Roche, Lilly, Loxo/Lilly, MedImmune, MSD, Novartis, Partner Therapeutics, QED Therapeutics, Relay Therapeutics, Surface Oncology, and Taiho Pharmaceutical; and travel accommodations from AstraZeneca and Merck. AV additionally reports honoraria from Advanced Accelerator Applications/Imaging Equipment Ltd, Amgen, AstraZeneca/MedImmune, BeiGene, Boehringer Pharma GmbH, Boston Scientific, Bristol Myers Squibb, Daichi-Sankyo, Eisai, GlaxoSmithKline, Incyte, Ipsen, Janssen, Lilly, MSD, Pierre Fabre, Roche, SERVIER, Sirtex Medical, Sirtex Medical, Taiho Oncology, and TERUMO; consulting or advisory fees from Amgen, AstraZeneca, Baxalta, Boehringer Pharma GmbH, BTG, Daichi-Sankyo, EISAI, Incyte, IPSEN, Lilly, Novartis, Pierre Fabre, Roche, Sirtex Medical, Taiho Oncology, Taiho Oncology, and Terumo; research funding from Novartis; and travel accommodations from AstraZeneca, Ipsen, Lilly, MSD, and Roche. JF additionally reports honoraria from Astellas Pharma, AstraZeneca, Bayer Yakuhin, Chugai Pharma, Daiichi Sankyo, EA Pharma, Eisai, Fujifilm, Incyte Japan, Lilly Japan, Merck, MSD, Nihon Servier, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Teijin Pharma, and Yakult Honsha; consulting or advisory fees from Astellas Pharma, AstraZeneca, Chugai Pharma, Delta-Fly Pharma, Eisai, Fujifilm, J-Pharma, Merck, MSD, OncoTherapy Science, and Ono Pharmaceutical; and research funding to their institution from Astellas Pharma, AstraZeneca, Chugai Pharma, Daiichi Sankyo, Delta-Fly Pharma, Eisai, J-Pharma, MSD, Ono Pharmaceutical, Sumitomo Dainippon, Taiho Pharmaceutical, Takeda, and Yakult Honsha. ZR additionally reports consulting or advisory fees from AstraZeneca, BeiGene, F. Hoffmann LaRoche, Innovent Biologics, and MSD. TY additionally reports honoraria from AstraZeneca, Bristol Myers Squibb, and MSD Oncology; and consulting or advisory fees from Bristol Myers Squibb. SLC additionally reports honoraria from AstraZeneca, Eisai, Ipsen, MSD, and Roche; consulting or advisory fees from AstraZeneca, BMS, Eisai, MSD Oncology, and Roche; and research funding from Eisai, Ipsen, and MSD. MO additionally reports honoraria from AstraZeneca, Bayer, Eisai, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, and Yakult Honsha. JOP additionally reports consulting or advisory fees from ABL Bio, Adicet Bio, AstraZeneca, Celgene, ImmuneOncia, Intocell, MediRama, Merck Serono, and SERVIER; research funding from ABL Bio, Celgene, Eutilex, medpacto, and SERVIER; and travel accommodations from Minneamrita Therapeutics. JWV additionally reports consulting or advisory fees from Aptitude Health, AstraZeneca, Autem Medical, Baxter, Boehringer Ingelheim, Cantargia AB, Debiopharm Group, Genoscience Pharma, Hutchison MediPharma, Imaging Equipment Limited, Incyte, Ipsen, Keocyt, Medivir, Merck, Mundipharma, Novartis, Nucana, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED Therapeutics, SERVIER, Sirtex Medical, Taiho Oncology, Wren Laboratories, and Zymeworks; speakers' bureau fees from Delcath Systems, Imaging Equipment Limited, Incyte, Ipsen, Mylan, Novartis, Nucana, and SERVIER; and travel accommodations from AstraZeneca/MedImmune, Lilly, Nucana, and Roche. JE additionally reports consulting or advisory fees from AstraZeneca, Basilea, Bayer, BeiGene, Boston Scientific, Bristol Myers Squibb, BTG, Eisai, Ipsen, Merck Serono, MSD, Roche, SERVIER, and Taiho Oncology; research funding to their institution from BeiGene, Boston Scientific, and Bristol Myers Squibb; and travel accommodations from Amgen, Bristol Myers Squibb, and Roche. SK, JMN, LY, and UM additionally report salary for full-time employment from MSD and stock ownership in MSD. RSF additionally reports consulting role from AstraZeneca, Bayer, Bristol Myers Squibb, CStone Pharmaceuticals, Eisai, Exelixis, Genentech/Roche, Hengrui Therapeutics, Lilly, Merck, and Pfizer; speakers' bureau fees from Genentech; and research funding to their institution from Bayer, Bristol Myers Squibb, Eisai, Lilly, Merck, Novartis, Pfizer, and Roche/Genentech. SCO, SG, and JGK report no additional competing interests.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Medical
Research Materials
