Efficacy and safety of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in advanced biliary tract cancer

Chengpei Zhu, Jingnan Xue, Yunchao Wang, Shanshan Wang, Nan Zhang, Yanyu Wang, Longhao Zhang, Xu Yang, Junyu Long, Xiaobo Yang, Xinting Sang, Haitao Zhao, Chengpei Zhu, Jingnan Xue, Yunchao Wang, Shanshan Wang, Nan Zhang, Yanyu Wang, Longhao Zhang, Xu Yang, Junyu Long, Xiaobo Yang, Xinting Sang, Haitao Zhao

Abstract

Background: Lenvatinib combined with anti-PD-1 antibodies and systemic chemotherapy has demonstrated a relatively high antitumor activity for intrahepatic cholangiocarcinoma in phase 2 clinical trials. However, its efficacy and safety in advanced biliary tract cancer (BTC) has not been reported in a real-world study.

Methods: Patients with advanced BTC who received lenvatinib combined with PD-1/PD-L1 inhibitors plus oxaliplatin and gemcitabine (Gemox) chemotherapy were retrospectively screened. The overall survival, progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety were evaluated.

Results: Fifty-seven patients with advanced BTC were included in the study. The median follow-up time was 15.1 (95% CI: 13.6-19.7) months. The median overall survival and progression-free survival were 13.4 (95% CI: 10.0-NA), and 9.27 (95% CI: 7.1-11.6) months, respectively. The objective response rate, disease control rate and clinical benefit rate were 43.9% (95% CI: 31.8%-56.7%), 91.2% (95% CI: 81.1%-96.2%), and 73.7% (95% CI: 61.0%-83.4%), respectively. Subgroup analysis revealed that the first-line treatment group had a longer median progression-free survival (12.13 vs. 6.77 months, P<0.01) and median overall survival (25.0 vs. 11.6 months, P=0.029) than the non-first-line treatment group. Moreover, three patients underwent conventional surgery after treatment. All patients (100%) experienced adverse events, and 45.6% (26/57) experienced grade 3 or 4 adverse events. The most commonly observed grade 3 or 4 adverse events was myelosuppression (7/57, 12.3%). No grade 5 adverse events were reported.

Conclusion: Lenvatinib combined with PD-1/PD-L1 inhibitors and Gemox chemotherapy represents an effective and tolerable treatment option in patients with advanced BTC.

Keywords: Gemox chemotherapy; PD-1 inhibitor; PD-L1 inhibitor; advanced biliary tract cancer; lenvatinib.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2023 Zhu, Xue, Wang, Wang, Zhang, Wang, Zhang, Yang, Long, Yang, Sang and Zhao.

Figures

Figure 1
Figure 1
Flow diagram of study design.
Figure 2
Figure 2
Therapeutic efficacy and treatment distribution of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in patients with advanced biliary tract carcinoma (A)Duration of patients’ treatments. (B)Maximum percentage change in the sum of the diameters of the target lesions from baseline. (C)Kaplan-Meier estimation of progression-free survival of the entire cohort. (D)Kaplan–Meier estimation of overall survival of the entire cohort. *First response was defined as the first time assessed as partial or complete response.
Figure 3
Figure 3
The progression-free survival and overall survival in subgroup analyses (A) Subgroup analyses of progression-free survival (PFS) and overall survival (OS) in the entire cohort. Kaplan-Meier plot for PFS (B) and OS (C) based on first-line treatment group compared with the non-first-line treatment group. Kaplan-Meier plot for PFS (D) and OS (E) based on PD-L1 positive expression group compared with PD-L1 negative expression group.
Figure 4
Figure 4
Frequency of any grade and grade 3/4 adverse events.

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