Chemotherapy and targeted therapy for advanced biliary tract cancers：An umbrella review

Abstract

Background: Malignant tumors of the biliary system have high malignancy and strong invasiveness, and are usually found in late stages with poor prognosis. For patients with advanced biliary tract cancer, chemotherapy and targeted therapy are one of the options to improve prognosis and delay tumor progression. The purpose of this study was to comprehensively evaluate the safety and efficacy of various chemotherapy regimenfor advanced biliary carcinoma. Methods : An umbrella review method was adopted, which aims to summarize the evidence from multiple studies around a research topic. Evidence from meta analyses up to 09 April 2022 were identified using PubMed, Web of Science, the Cochrane database, as well as manual screening. Eligible studies were screened according to inclusion and exclusion criteria. This study had been registered at PROSPERO (CRD42022324548).For each eligible study, we extracted the data of general characteristics and the main findings. The methodological quality of the included studies were assessed by AMSTAR2 and the quality of evidence was evaluated by the GRADE. Results : A total of 1833 articles were searched, 14 unique articles with 94 outcomes were identified by eligibility criteria. The incidence of skin rash (RR=18.11,95%CI 5.13-63.91) and diarrhea (RR=2.48,95%CI 1.2-5.10) was higher in patients receiving gemcitabine-based chemotherapy plus targeted therapy than in patients receiving gemcitabine alone. Patients receiving gemcitabine-containing chemotherapy developed leukopenia (OR=7.17, 95%CI 1.43-36.08), anemia (OR=7.04, 95%CI 2.59-19.12), thrombocytopenia (RR=2.45, 95%CI 1.39-4.32) and neutropenia (RR=3.30, 95%CI 1.04-10.50) were significantly higher than gemcitabine-free regimens. In addition, patients receiving S-1 monotherapy had significantly better ORR (RR=2.46,95%CI 1.27-4.57) than patients receiving S-1+gemcitabine. Patients receiving fluoropyrimidine-based chemotherapy had longer OS (HR=0.83, 95%CI 0.7-0.99), higher DCR (0R=5.18, 95%CI 3.3-10.23), and higher ORR (0R=3.24, 95%CI 1.18-8.92) compared with 5-FU/LV monotherapy or supportive therapy. Surprisingly, there was also evidence that gemcitabine-based chemotherapy did not improve postoperative patients' OS (HR=0.91, 95%CI 0.74-1.12) when compared with best supportive care. Conclusions: This study comprehensively evaluated the safety and efficacy of chemotherapy or targeted therapy regimens for advanced biliary tract cancer and found 11 "moderate" or "high" levels of evidence, however, most of the evidence was still at "low" or "very low" levels. More randomized controlled studies are needed in the future to further summarize high-level evidence.