A systematic review and network meta-analysis of adjuvant therapy for curatively resected biliary tract cancers.

Abstract

247 Background: Although recently completed randomized controlled trials (RCTs) have added high-quality data regarding adjuvant therapy in curatively resected biliary tract cancer (BTC), there is still no standard approach to manage these patients. We conducted a systematic review and network meta-analysis to compare the efficacy of adjuvant therapy regimens in curatively resected BTC to help guide clinical decision making and the design of future prospective trials. Methods: We conducted a systematic review of published studies and abstracts up to and including June 2018. Studies were included if they were phase III RCTs on patients with histologically proven BTC receiving adjuvant chemotherapy after a complete surgical resection (R0 or R1). BTCs included gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma. The endpoints of interest were overall survival (OS) and relapse-free survival (RFS). Network meta-analysis methods were used for indirect comparison between adjuvant therapy regimens. Results: Five RCTs were included in the qualitative synthesis and three RCTs (BILCAP, PRODIGE 12-ACCORD 18 and BCAT) included sufficient data to be included in the meta-analysis. Results from the indirect comparison demonstrated no significant difference in OS between any of the adjuvant therapy regimens, however there was a trend that favoured adjuvant therapy with capecitabine over gemcitabine or gemcitabine plus oxaliplatin (GEMOX), with hazard ratios (HRs) of 0.82 (95% CI, 0.53-1.27) and 0.86 (95% CI, 0.56-1.34), respectively. Similarly there was no significant improvement in RFS with capecitabine compared to gemcitabine or GEMOX with HRs of 0.82 (95% CI, 0.53-1.27) and 0.86 (95% CI, 0.56-1.34), respectively. Conclusions: Although capecitabine is considered to be standard of care in the adjuvant setting based on a single randomized phase III study, in this indirect comparison, we did not find a statistically significant improvement in OS or RFS with capecitabine compared to GEMOX or gemcitabine. Further prospective trials comparing adjuvant therapies to capecitabine are warranted.