The faculty review patient-reported outcomes, subgroup consistency, and biomarker testing before introducing the second pivotal trial. Health-related quality of life in TOPAZ-1 was assessed, and the panel reports no clinically meaningful detriment in quality of life with the addition of durvalumab across global health status, functional domains, or symptom scores, with the adjusted mean change from baseline in global health status and quality of life was higher with the durvalumab arm. The long-term safety update identified no new safety signals and no additional adverse events leading to treatment discontinuation. Turning to subgroups, the faculty note that the overall survival benefit was consistent across disease status and across primary tumor location. PD-L1 expression was not meaningful for benefit in the study, and the panel concludes that PD-L1 testing has no role in selecting candidates for chemoimmunotherapy and that no validated biomarker is currently available for patients with advanced biliary tract cancer. The segment then introduces KEYNOTE-966, a phase 3, randomized, double-blind, placebo-controlled trial conducted across a large international network of centers in patients with unresectable locally advanced or metastatic disease and good performance status, stratified by region, disease stage, and site of origin. The faculty highlight the key design difference from TOPAZ-1, namely that gemcitabine could be continued until progression rather than stopped at a fixed number of cycles. They discuss how that maintenance strategy maps to standard practice in their region.
