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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2023-09, Vol.72 (9), p.2949-2960
• Main Authors: Zhu, Chengpei, Li, Hu, Yang, Xiaobo, Wang, Shanshan, Wang, Yunchao, Zhang, Nan, Wang, Yanyu, Xue, Jingnan, Zhang, Longhao, Ning, Cong, Yang, Xu, Xun, Ziyu, Chao, Jiashuo, Long, Junyu, Sang, Xinting, Zhu, Zhenyu, Zhao, Haitao
• Format: Article
• Language: English
• Subjects: Antitumor agents; Apoptosis; B7-H1 Antigen; Bile Duct Neoplasms - drug therapy; Bile Ducts, Intrahepatic; Biliary tract; Biliary tract diseases; Cancer Research; Cell death; Chemotherapy; Cholangiocarcinoma; Cholangiocarcinoma - drug therapy; Clinical trials; Disease control; Humans; Immune Checkpoint Inhibitors; Immunology; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Multivariate analysis; Myelosuppression; Oncology; Patients; PD-1 protein; PD-L1 protein; Prognosis; Retrospective Studies; Safety; Tumors
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-023-03466-8

Background A programmed cell death protein-1 (PD-1) inhibitor combined with lenvatinib and Gemox chemotherapy as first-line therapy demonstrated high anti-tumor activity against biliary tract cancer in phase II clinical trials. Herein, we aimed to investigate the efficacy and safety for advanced intrahepatic cholangiocarcinoma (ICC) in a multicenter real-world study. Methods Patients with advanced ICC who received PD-1 inhibitor combined with lenvatinib and Gemox chemotherapy were retrospectively screened at two medical centers. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors for survival were analyzed. Results Fifty-three patients with advanced ICC were included in this study. The median follow-up time was 13.7 (95% confidence interval (CI): 12.9–17.2) months. The median OS and PFS were 14.3 (95% CI: 11.3–NR) and 8.63 (95% CI: 7.17–11.6) months, respectively. The ORR, DCR, and clinical benefit rate were 52.8, 94.3, and 75.5%, respectively. In the multivariate analysis, the tumor burden score (TBS), tumor-node metastasis classification (TNM) stage, and PD-L1 expression were independent prognostic factors for OS and PFS. All patients experienced adverse events (AEs), 41.5% (22/53) experienced grade 3 or 4 AEs, including fatigue (8/53, 15.1%) and myelosuppression (7/53, 13.2%). No grade 5 AEs were reported. Conclusion PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy represent an effective and tolerable regimen for advanced ICC in a multicenter retrospective real-world study. TBS, TNM stage, and PD-L1 expression can be used as potential prognostic factors for OS and PFS.