The combination of programmed cell death protein-1 (PD-1) inhibitors along with lenvatinib and gemcitabine-oxaliplatin (Gemox) chemotherapy was effective and tolerable as a treatment for advanced intrahepatic cholangiocarcinoma (CCA), according to a study published in Cancer Immunology, Immunotherapy.

Patients in the multicenter, retrospective real-world study experienced an objective response rate of 52.8%, a disease control rate of 94.3%, and a clinical benefit rate of 75.5% over a median follow-up time of 13.7 months.

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The median overall survival and progression-free survival were 14.3 and 8.63 months, respectively, and patients had a median duration of treatment of 8.07 months.

Out of the 53 patients enrolled in the study, 36 (67.9%) experienced decreased tumor sizes compared to baseline as observed through imaging. An objective response was observed in 28 patients (52.7%) including a complete response in 3 (5.7%) and a partial response (PR) in the remaining 25 (47.1%). Stable disease was observed in 22 (41.5%) patients while progressive disease was only observed in 3 (5.7%) patients.

Conversion surgery was administered to 6 patients – 4 who had achieved PR and 2 who achieved complete response prior to surgery. No disease progression was observed in 5 of the patients at the time of last follow-up and they were receiving maintenance therapy with a PD-1 inhibitor and lenvatinib. One of these patients experienced disease progression after 1.2 months post-surgery and changed treatment regimes.

All 53 participants experienced adverse events (AEs) during the study but only 22 (41.5%) patients experienced AEs of grade 3 or greater and 1 (1.9%) patient experienced grade 4 AEs. No patient experienced grade 5 AEs. The most common AEs were fatigue (58.5%), myelosuppression (26.4%), and decreased appetite (22.6%).

“In conclusion, PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy are effective, safe, and well-tolerated as first-line therapies for advanced [intrahepatic CCA],” the authors wrote.

In subgroup analysis, 3 potential prognostic factors were identified including tumor burden score, tumor-node metastasis classification staging, and PD-L1 expression. Patients tended to have longer median overall survival and PFS with a tumor burden score less than 8 compared to those with a score greater or equal to 8; tumor-node metastasis classification stage 3 vs stage 4; and positive PD-L1 expression than those with negative PD-L1 expression (P <.001 for all).


Zhu C, Li H, Yang X, et al. Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study. Cancer Immunol Immunother. Published online May 29, 2023. doi:10.1007/s00262-023-03466-8