Abstract
OBJECTIVE: To determine the most ideal second-line treatment for advanced biliary tract cancer, considering the response rate, survival, and drug adverse events. METHODS: This network meta analysis (NMA) was conducted in accordance with the PRISMA with NMA extension guidance. After formulation of PICO, comprehensive searches of literatures were done including all randomized controlled studies that reported the second-line treatment for advanced biliary tract cancers' subjects who have failed with first-line gemcitabine-based chemotherapy. The outcomes analyzed were response rate, progression-free survival, overall survival, and serious adverse events. Data were collected and analysis will be done based on Bayesian method using BUGSnet package in R studio. RESULTS: Eleven eligible RCTs were included in this NMA with 1228 subjects and 15 different second-line therapies. The NMA was conducted in random-effects, consistent, and convergence model. Most studies reported the use of fluoropyrimidine-based regimen, either alone or in combination with others drugs. The combination of 5FU-LV with liposomal irinotecan showed the most favorable outcomes, the highest response rate, longest overall survival, and longest progression-free survival. However, this regimen had highest adverse events among others. The next promising regimen was combination of oral capecitabine with varlitinib, with favorable response rate (RR 16.67; 95%CI 0.01 to 21.39), overall survival (HR 0.09; 95%CI -5.22 to 5.37), and progression-free survival (HR 1.37; 95%CI -58.4 to 62.15). The serious adverse events were reported less than others. CONCLUSION: The combination of oral capecitabine with varlitinib could be a promising second-line treatment for patients with advanced biliary tract cancer refractory to gemcitabine-based first-line regimen.