Targeted and immunotherapy strategies in biliary tract cancer: A Bayesian network meta-analysis comparing efficacy and safety.

Abstract

141 Background: Biliary tract cancer is an aggressive malignancy with limited treatment options and poor prognosis. Advances in targeted therapy and immune checkpoint inhibition have expanded systemic treatment strategies, yet comparative evidence remains limited. This study aimed to evaluate and compare the efficacy and safety of VEGFR inhibitors, FGFR inhibitors, IDH1 inhibitors, PD-1/PD-L1 inhibitors, chemotherapy, and placebo. The primary objective was to rank treatments based on objective response rate (ORR), while the secondary objective assessed safety using adverse event (AE) outcomes. Methods: Randomized controlled trials were systematically identified. A Bayesian network meta-analysis was conducted using MetaInsight. Treatment effects were estimated using pooled odds ratios with Markov chain Monte Carlo simulations. Ranking probabilities and surface under the cumulative ranking curve (SUCRA) values were calculated to compare efficacy (ORR) and safety (adverse events) across treatments. Results: For efficacy, VEGFR inhibitors ranked highest (SUCRA 92.10), followed by FGFR inhibitors (74.92) and cisplatin plus gemcitabine (55.35). PD-1/PD-L1 inhibitors (19.24) and placebo (8.39) demonstrated lower ORR rankings. VEGFR inhibitors had the greatest probability of being best (82%), while FGFR inhibitors most frequently ranked second (70%). For safety, VEGFR inhibitors also ranked highest (SUCRA 95.31), followed by IDH1 inhibitors (54.98), PD-1/PD-L1 inhibitors (34.40), and placebo (15.31). VEGFR inhibitors showed a 90% probability of being safest. These findings suggest that VEGFR-targeted therapy provides a favorable balance between efficacy and safety. FGFR inhibitors also demonstrated strong efficacy performance, while IDH1 inhibitors showed moderate safety advantages. PD-1/PD-L1 inhibitors exhibited comparatively lower efficacy with intermediate safety. Despite heterogeneity across studies, consistent SUCRA trends support robustness of the results. Conclusions: VEGFR inhibitors demonstrate the most favorable balance of efficacy and safety, followed by FGFR inhibitors in efficacy and IDH1 inhibitors in safety. These findings provide comparative evidence to support treatment selection in biliary tract cancer, although further direct head-to-head trials are warranted to confirm these results.