Effectiveness and safety of PD-1/PD-L1 inhibitors plus lenvatinib with or without Gemox chemotherapy in advanced intrahepatic cholangiocarcinoma

Advanced intrahepatic cholangiocarcinoma (ICC) is characterized by a poor prognosis. This study evaluated the efficacy and safety of programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors combined with lenvatinib, with or without gemcitabine and oxaliplatin (Gemox) chemotherapy. A retrospective cohort analysis was performed on patients with advanced ICC who received treatment with PD-1/PD-L1 inhibitors and lenvatinib, with or without Gemox chemotherapy, between February 2017 and February 2024. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. The study included 107 patients, comprising 67 patients treated with PD-1/PD-L1 inhibitors and lenvatinib (P-L group) and 40 patients treated with PD-1/PD-L1 inhibitors, lenvatinib, and Gemox chemotherapy (P-L-G group). In comparison to the P-L group, the P-L-G group had longer median OS (16.4 months vs. 13.7 months, P = 0.047) and median PFS (11.1 months vs. 5.6 months, P = 0.004). Furthermore, the P-L-G group had a higher ORR (60.00% vs. 22.39%) and DCR (85.00% vs. 73.13%). All patients experienced adverse events (AEs), with 33 patients (49.25%) in the P-L group and 22 patients (55.00%) in the P-L-G group reporting grade 3–4 AEs. No grade 5 AEs were observed, and all AEs were manageable. Meanwhile, among patients with TP53 mutations ( P = 0.048), KRAS mutations ( P = 0.037), IDH1 mutations ( P = 0.033), or BAP1 wild-type status ( P = 0.039 and P = 0.022), the P-L-G group exhibited a more favorable prognosis compared to the P-L group. Advanced ICC patients may derive greater benefit from the triple combination therapy of PD-1/PD-L1 inhibitors, lenvatinib, and Gemox chemotherapy without an increase in AEs. This regimen holds potential as an effective first-line treatment for advanced ICC.