Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer.

Background: Lenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC).

Methods: Patients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety.

Results: A total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2-20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2-26.9) and 6.1 (95% CI: 4.9-7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil-lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported.

Conclusion: Anti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.