Efficacy of regorafenib in patients with advanced biliary tract cancer: An updated systematic review and meta-analysis.

Abstract

584 Background: Biliary tract cancer (BTC), or cholangiocarcinoma, is an aggressive and fatal malignancy that forms in the bile ducts. BTCs, although rare, carry a poor prognosis with limited options for treatment, especially when advanced. Various modalities of therapy have emerged with improvement in cancer diagnosis, including multi-kinase inhibitors which work by blocking multiple steps crucial for tumor growth and metastatic progression. Regorafenib, a tyrosine-kinase inhibitor, has been employed either as monotherapy (MT) or in combination (CT) with other agents with questionable efficacy. This research aims to answer the efficacy of regorafenib in the management of patients with advanced BTC. Methods: A comprehensive literature search was performed across PubMed, Embase, and the Cochrane Library. Studies reporting efficacy outcomes of Regorafenib monotherapy or combination regimens in advanced BTC patients were included. Meta-analyses of pooled proportions were conducted using random-effects models along with transformation of raw data to maintain statistical robustness. Statistical heterogeneity was assessed using the I² statistic. All analyses were performed in R version 4.4.2. Results: Six studies encompassing a total of 219 patients were included in the study. CT showed consistency across all the outcomes, with pooled Overall Survival of 15.12 months (95% CI: 11.66 - 18.57), while MT showed variability, 17.98 months (95% CI: -3.80 - 39.76), however both groups demonstrated high heterogeneity (I2>95%). The Progression Free Survival was more favorable with CT at 8.45 months (95% CI: 3.06 - 13.83)(I² = 99.7%) compared to MT, 8.11 months (95% CI: -0.79 to 17.01)(I² = 99.8%). Overall Response Rate was higher with CT (~50%) compared to MT (~10%), while Complete Response and Partial Response were comparable across both groups (3.3% vs 1.3%) and (~33% vs 9.4%). Similarly, the disease progression was favorable in CT as well (21.6% vs 63.4%). However, no statistically significant subgroup differences were identified across outcomes. Conclusions: This meta-analysis suggests that regorafenib monotherapy demonstrates modest efficacy in patients with advanced BTC, with greater activity observed in combination regimens. These findings demonstrate the potential role of regorafenib in addressing the therapeutic gap potentially extending survival in patients with limited alternatives. Larger, prospective randomized trials are warranted to further define and optimize the clinical benefit of regorafenib in both MT and CT regimens.