Lenvatinib plus PD-1 inhibitors combined with chemotherapy versus lenvatinib plus PD-1 inhibitors for unresectable or recurrent biliary tract cancer

Background Lenvatinib and programmed cell death-1 (PD-1) inhibitors have emerged as a novel treatment for patients with BTC. This study aimed to compare the efficacy and safety of triple therapy with lenvatinib, PD-1 inhibitors plus chemotherapy (LenP + C) and dual therapy with lenvatinib plus PD-1 inhibitors (LenP) in patients with unresectable or recurrent BTC. Methods BTC patients receiving LenP + C or LenP treatment between June 2020 and March 2022 were retrospectively analyzed. The primary outcome was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results Ninety-eight patients were included in the present study, and they were divided into the LenP + C group (n = 40) and LenP group (n = 58). The median PFS was 8.3 months in the LenP + C group, significantly longer than 4.5 months in the LenP group (HR = 0.471; 95% CI, 0.271–0.817; P = 0.007). Although no difference was found in ORR between the two groups (LenP + C, 42.5% vs. LenP, 27.6%, P = 0.125), the DCR was higher in the LenP + C group than in the LenP group (95.0% vs. 75.9%, P = 0.012). The median OS was comparable between the two groups (13.7 vs. 12.4 months, P = 0.749). Treatment-related adverse events were more frequently observed in the LenP + C group. The incidence of neutropenia (grade ⩾3) was higher in patients receiving triple therapy (15% vs. 2%, P = 0.035). Conclusions This study showed that treatment with lenvatinib and PD-1 inhibitors is safe and effective for advanced BTC. The combination of chemotherapy with lenvatinib and PD-1 inhibitors showed improved anti-tumor efficacy compared with lenvatinib and anti-PD-1 therapy, yet with more toxic effects.