Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials

In this pre-planned meta-analysis (of individual patient-level data) from two prospective randomised studies (UK: ABC-02 and Japan: BT22), investigators confirm the role of cisplatin / gemcitabine as first-line chemotherapy in 494 patients with advanced biliary tract cancer with greater statistical power. Moreover, the magnitude of benefit is the same between these different ethnic populations.Two recent studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone for patients with pathologically proven advanced biliary tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). This pre-planned analysis evaluates the efficacy of CisGem with increased statistical power. We carried out a meta-analysis of individual patient-level data of these studies to establish the effect of CisGem versus Gem on progression-free survival (PFS), overall survival (OS) and carried out exploratory subgroup analyses. CisGem demonstrates a significant improvement in PFS [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.53-0.76, P < 0.001] and OS (HR = 0.65, 95% CI 0.54-0.78, P < 0.001) over Gem. This effect is most marked among patients with good performance status (PS 0-1): HR for PFS is 0.61 (95% CI 0.51-0.74), P < 0.001 and OS HR = 0.64 (95% CI 0.53-0.77), P < 0.001. CisGem resulted in improved PFS and OS for intra- and extra-hepatic cholangiocarcinomas and gallbladder cancer. The treatment effect between UK and Japanese patients was consistent with respect to OS (HR = 0.65, 95% CI 0.53-0.79 and 0.65, 95% CI 0.42-1.03, respectively); with similar OS in the combination arms (median 11.7 and 11.1 months, respectively). Subgroups least likely to benefit included patients with ampullary tumours and poor performance status (PS2). CisGem is the standard of care for the first-line treatment of good-PS patients with advanced BTC regardless of ethnicity. Future studies should aim to enhance the effectiveness of this regimen in the first-line setting, establish the role of subsequent (second-line) therapy and assess the role of rationally developed molecular-targeted therapies.