Background: In the randomized, double-blind, phase 3 KEYNOTE-966 trial (N = 1069; NCT04003636), pembro + gem/cis significantly improved OS versus placebo + gem/cis (HR 0.83; 95% CI 0.72-0.95; P = 0.0034) and had an expected and manageable safety profile as first-line therapy for unresectable locally advanced or metastatic BTC. We present the protocol-specified exploratory patient-reported outcomes (PROs) from KEYNOTE-966. Methods: PROs were assessed using the EORTC QLQ-C30, EORTC QLQ-BIL21, and EQ-5D-5L questionnaires. The analysis population included all treated patients (pts) who completed ≥1 HRQoL assessment for the specific endpoint. A constrained longitudinal analysis model (covariates: treatment, time, treatment by time interaction, and stratification factors) was used to compare least squares mean (LSM) score changes from baseline (BL) to wk 18 (ie, latest timepoint that completion was ≥60% and compliance was ≥80%) in QLQ-C30 global health status (GHS)/QoL, physical functioning (PF), and role functioning (RF), QLQ-BIL21 jaundice and pain, and EQ-5D-5L visual analogue scale (VAS). A stratified Cox proportional hazards model was used to assess the magnitude of the between-arm difference in time to deterioration (TTD) in GHS/QoL, PF, RF, jaundice, and pain (ie, time to first onset of ≥10-point deterioration from BL in each scale/subscale confirmed by ≥10-point deterioration from BL at the next visit; established as clinically relevant). Results: Questionnaire compliance was >87% from BL to wk 18 in both arms. LSM changes from BL to wk 18 in QLQ-C30 GHS/QoL, PF, and RF, QLQ-BIL21 jaundice and pain, and EQ-5D-5L VAS were similar between arms. Time to deterioration was also similar between arms: median not reached (NR) vs 21.2 mo for GHS/QoL (HR 0.86, 95% CI 0.70-1.07), NR vs 12.0 mo for PF (HR 0.95, 95% CI 0.78-1.17), 6.5 mo vs 5.8 mo for RF (HR 0.98, 95% CI 0.81-1.18), NR vs NR for jaundice (HR 1.20, 95% CI 0.94-1.54), and NR vs NR for pain (HR 0.79, 95% CI 0.59-1.05). Conclusions: HRQoL was maintained when pembro was added to gem/cis. Together with the efficacy and safety data, these results support pembro + gem/cis as a new first-line treatment option for advanced BTC. Clinical trial information: NCT04003636.

Higher GHS/QoL and functioning scores indicate improvement. Lower symptom scores indicate improvement.