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

Abstract

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.

The fibrosis-4 index is a prognostic factor for cholangiocarcinoma patients who received immunotherapy

“…Notably, one patient receiving sintilimab discontinued treatment due to severe bone marrow suppression (grade 4). According to a multicenter study that included 53 patients, researchers reported that all patients experienced irAEs (30). Fatigue, both in any grade and grade 3 or higher, was the most common adverse event, with 41.5% of patients experiencing severe (grade 3 or higher) reactions, and one case of grade 4 bone marrow suppression, findings similar to those of our study.…”

Case Report: Camrelizumab combined with gemcitabine and oxaliplatin in the treatment of advanced intrahepatic cholangiocarcinoma: a case report and literature review

“…(B) CA19-9 levels before and after chemotherapy. 11.6) months, respectively (33). These results suggest that the combination of ICIs with chemotherapy and TKIs is another promising approach for the treatment of ICC, which will be investigated in future clinical studies.…”

“…Zhu et al. investigated the efficacy of PD-1 inhibitors combined with TKI lenvatinib and GEMOX chemotherapy as first-line treatment in advanced ICC, and reported a median OS and progression-free survival of 14.3 (95% CI: 11.3–not reached) and 8.63 (95% CI: 7.17–11.6) months, respectively ( 33 ). These results suggest that the combination of ICIs with chemotherapy and TKIs is another promising approach for the treatment of ICC, which will be investigated in future clinical studies.…”

Editorial: Advances in immunotherapy and combination therapy for biliary tract cancers

“…Chemotherapy may not only up-regulate checkpoint expression and alter immune cell infiltration, it also works by disrupting strategies used by tumors to evade immune recognition. The results of several clinical trials and real-world studies suggest that the addition of targeted therapies to immune-combination chemotherapy is a promising approach for the treatment of BTC, but is also challenged by the high incidence of adverse effects ( 1 – 4 ). Wang et al.…”

“…Chemotherapy may not only up-regulate checkpoint expression and alter immune cell infiltration, it also works by disrupting strategies used by tumors to evade immune recognition. The results of several clinical trials and real-world studies suggest that the addition of targeted therapies to immune-combination chemotherapy is a promising approach for the treatment of BTC, but is also challenged by the high incidence of adverse effects (1)(2)(3)(4). Wang et al reported a case of progressive ICC with poor results of first-line chemotherapy, which was treated with ICI plus tyrosine kinase inhibitor combined with radiotherapy in the second line to achieve better efficacy.…”