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

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.