This retrospective study of 1,358 patients with advanced biliary tract cancer (BTC) treated with first-line cisplatin, gemcitabine, and durvalumab across 55 centers in 12 countries evaluated whether matched targeted therapy (vs. non-targeted active treatment) improved outcomes after chemoimmunotherapy failure, and whether the line of therapy (2nd vs. 3rd line) influenced benefit.
Among 125 patients receiving active post-progression treatment, matched targeted therapy was associated with significantly longer OS (median 24.8 vs. 16.6 months; adjusted HR 0.35, 95% CI 0.22–0.56; p<0.0001). In second line specifically (n=127), matched therapy improved OS (HR 0.50), PFS (5.9 vs. 3.2 months; HR 0.60), and ORR (27.1% vs. 9.1%); no significant benefit was seen in third line. However, only 32% (76/238) of patients with actionable alterations actually received matched therapy.
Retrospective design limits causal inference; subgroup sizes for individual molecular alterations were small, precluding alteration-specific conclusions; fewer than one-third of eligible patients received matched therapy in routine care, suggesting access gaps that may have introduced selection bias.
Clinicians should pursue early and systematic molecular profiling—ideally before first-line progression—so patients with actionable alterations (ESCAT tier I) can access matched targeted therapy in second line, where the survival benefit appears greatest. Waiting until third line does not appear to confer the same benefit.
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