Anti-cancer drugs versus supportive care for advanced biliary tract cancers: a systematic review

Abstract

Introduction Biliary tract cancers (BTCs) have low survival rates in advanced stages. Anticancer drugs (ACDs) are usually recommended, but may be associated with important toxicity and lower quality of life (QoL). Best supportive care (BSC) could represent a valid alternative of treatment. We aim to synthesise evidence regarding the effects of ACDs versus BSC in patients with advanced BTCs. Methods We conducted a systematic review including randomised controlled trials (RCTs) comparing any type of ACD versus BSC, placebo or no active treatment. We searched in five databases. Two reviewers performed selection, risk of bias and data extraction processes. We conducted random-effects meta-analyses and assessed certainty of evidence using GRADE. Results We included eight RCTs. Biological/targeted therapies may result in little to no difference in overall survival (OS) (Mean difference (MD): 1.66 months higher; 95%CI, -0.65 to 3.96; low certainty) and toxicity (Relative risk (RR): 1.38; 95%CI, 0.99 to 1.93; low certainty), with uncertain effects on QoL. Evidence is very uncertain about the effects of chemotherapy on OS (MD: 3.28 months higher; 95%CI, 0.16 to 6.39; very low certainty), and may increase toxicity (RR: 1.33; 95%CI, 1.03 to 1.72; low certainty). We identified insufficient evidence for other prespecified outcomes. Conclusions Compared to BSC, ACDs have poor OS benefit and higher toxicity. Due to overall very low certainty of evidence, the effects of ACDs on critical outcomes are still unclear. Our findings should be used to better inform decision-making processes and future research.