Survival outcomes with matched targeted therapy in advanced biliary tract cancer: a large global cohort analysis

The prognosis of advanced biliary tract cancer remains poor despite up to 40% of tumors harboring actionable molecular alterations. This international collaborative study from Mayo Clinic, Duke Cancer Institute, National Cancer Center East (Japan), and the SCRUM-Japan GOZILA/MONSTAR-SCREEN projects evaluated clinical outcomes in 1049 patients with advanced BTC based on tumor molecular profiling and matched treatment selection. Patients were categorized into non-actionable, actionable with matched targeted therapy (matched), and actionable without matched therapy (unmatched) groups. Among 358 patients (34.1%) with actionable alterations, 160 (44.7%) received matched therapy. The matched group demonstrated significantly longer median overall survival (23.3 months; 95% CI: 19.5–30.4) compared to unmatched (14.7 months; 95% CI: 12.8–17.9) and non-actionable groups (17.1 months; 95% CI: 15.5–18.7; HR 0.57, 95% CI: 0.46–0.71; p 0.0001). In 700 patients receiving ≥2 lines of therapy, matched therapy remained independently associated with improved survival (HR 0.62; 95% CI 0.43–0.90). Notably, patients with actionable tumors who did not receive matched therapy experienced worse outcomes than those with non-actionable disease. These findings highlight the critical need for universal molecular profiling and equitable access to targeted therapies in advanced BTC.