Health-related quality of life in participants with advanced biliary tract cancer from the randomized phase III KEYNOTE-966 study

초록

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 Gem-Cis+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. Clinical trial registration: NCT04924062. (c) 2025 European Association for the Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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