Prognostic Role of Adverse Events in a Worldwide Population of Patients with Biliary Tract Cancer Treated with Chemo-Immunotherapy.

backgroundBiliary tract cancers (BTCs) are aggressive malignancies with limited treatment options. The addition of durvalumab or pembrolizumab to cisplatin-gemcitabine improves overall survival (OS), but validated biomarkers of benefit remain limited. Immune-mediated adverse events (imAEs) have been proposed as treatment-emergent clinical correlates of immune activation.

methodsWe retrospectively analyzed an international cohort of patients with locally advanced or metastatic BTC treated with first-line cisplatin-gemcitabine plus durvalumab. Primary endpoints were OS and progression-free survival (PFS). The principal exposure was the occurrence of any imAE. A post hoc complete-case Cox model was adjusted for age, sex, primary tumor site, prior surgery, ECOG performance status, disease stage, albumin, bilirubin, and neutrophil-to-lymphocyte ratio (NLR); analyses of individual AEs were exploratory. Exact AE onset dates were not consistently available, precluding a reliable formal time-dependent exposure analysis.

resultsA total of 1358 patients were included; all received durvalumab, and 276 (20.3%) developed at least one imAE. In the fully baseline-adjusted model, any imAE remained associated with a lower risk of death (adjusted HR 0.72, 95% CI 0.57-0.92;

conclusionsTreatment-emergent imAEs may represent potential prognostic markers or clinical correlates of benefit, but they are not validated surrogate endpoints. Prospective studies with precise AE-onset capture are required.