Triple therapy in biliary tract cancers: GemOX plus immune checkpoint inhibitor in combination with lenvatinib or NGS-guided targeted therapy

Purpose The combination of gemcitabine-based chemotherapy and immune checkpoint inhibitors has a good efficacy in advanced biliary tract cancer (BTC). The multi-target TKI lenvatinib and NGS-guided targeted therapy are also promising in BTC treatment. This study aimed to explore the performance of GemOX plus sintilimab and TKI (either lenvatinib or by NGS-guided targeted therapy) for local advanced or metastatic BTCs. Methods This prospective single-arm study included patients with local advanced or metastatic BTCs and applied intravenous infusion of standard GemOX plus sintilimab and lenvatinib (no targetable gene alterations) or targeted therapy based on NGS (olaparib for BRCA1/2 mutation, dasatinib for IDH1/2 mutation, afatinib for EGFR amplification, lenvatinib for PDGFR and KIT mutation, and lenvatinib for FGFR/KIT mutation). Results From November 2020 to December 2021, 22 patients BTCs (6 GBC, 14 iCCA, 1 pCCA and 1 dCCA cases) were enrolled, with an average age of 58.4 years. Partial response (PR) was achieved in 10 cases, stable disease (SD) in 9 cases and progression disease (PD) in 3 cases (13.6%). The objective response rate (ORR) was 45.5%, and the disease control rate (DCR) was 86.4%. During the treatment, the incidence of adverse reactions was 81.8%, and the incidence of grade 3/4 adverse events was 9.09%. For 14 patients with NGS, 5 patients were treated by targeted therapy and there were 1 SD and 4 PR cases. For four patients with positive PD-L1 expression, the ORR was 100%. While among the three patients with super-progression markers such as RET, MDM2 and FGF14/STK24, there were two SD and one PD cases. Conclusion In patients with advanced BTCs, the combination of GemOX plus sintilimab and lenvatinib or NGS-guided targeted therapy showed promising ORR and DCR, especially for the patients with positive PD-L1 expression and targetable gene alterations.