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

ABSTRACT

BACKGROUND: Malignant tumors of the biliary system are characterized by a high degree of malignancy and strong invasiveness, and they are usually diagnosed at late stages with poor prognosis. For patients with advanced biliary tract cancer, chemotherapy and targeted therapy are two of the options available to improve prognosis and delay tumor progression. This study aimed to comprehensively evaluate the safety and effectiveness of various chemotherapy schemes for the treatment of advanced biliary tract cancer in published systematic reviews and meta-analyses (SRoMAs). METHODS: An umbrella review method was adopted, which aims to summarize the existing evidence from multiple studies around a research topic. SRoMAs up to April 9, 2022, were identified using PubMed, Web of Science, the Cochrane database, and 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 the AMSTAR2 scale, and the quality of evidence was evaluated by the GRADE tools. 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, GRADE Moderate) and diarrhea (RR = 2.48, 95% CI 1.2-5.10, GRADE Moderate) was higher in patients receiving gemcitabine-based chemotherapy plus targeted therapy than in patients receiving gemcitabine monotherapy. The number of patients receiving gemcitabine-based chemotherapy who developed leukopenia (OR = 7.17, 95% CI 1.43-36.08, GRADE Moderate), anemia (OR = 7.04, 95% CI 2.59-19.12, GRADE High), thrombocytopenia (RR = 2.45, 95% CI 1.39-4.32, GRADE Moderate), and neutropenia (RR = 3.30, 95% CI 1.04-10.50, GRADE Moderate) was significantly higher than that of patients who received gemcitabine-free regimens. In addition, patients receiving S-1 monotherapy had significantly better ORR (RR = 2.46, 95% CI 1.27-4.57, GRADE Moderate) than patients receiving S-1 + gemcitabine. Patients receiving fluoropyrimidine-based chemotherapy had longer OS (HR = 0.83, 95% CI 0.7-0.99, GRADE Moderate), higher DCR (0R = 5.18, 95% CI 3.3-10.23, GRADE Moderate), and higher ORR (0R = 3.24, 95% CI 1.18-8.92, GRADE Moderate) compared with patients who received 5-FU/LV monotherapy or supportive therapy. Surprisingly, we found evidence that gemcitabine-based chemotherapy did not improve postoperative patients' OS (HR = 0.91, 95% CI 0.74-1.12, GRADE Moderate) 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 outcomes with "Moderate" or "High" levels; however, most of the outcomes were still at "low" or "very low" levels. More randomized controlled studies are needed in the future to further summarize high levels of evidence.