Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma: A single-center, prospective, single-arm clinical trial

Yupeng Ren; Yuxuan Li; Mingbo Cao; Yongchang Tang; Feng Yuan; Gaoyuan Yang; Zhiwei He; Zheng Shi; Xiaorui Su; Zhicheng Yao; Meihai Deng

doi:10.21147/j.issn.1000-9604.2024.02.02

Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma: A single-center, prospective, single-arm clinical trial

Chin J Cancer Res. 2024 Apr 30;36(2):114-123. doi: 10.21147/j.issn.1000-9604.2024.02.02.

Authors

Yupeng Ren¹, Yuxuan Li¹, Mingbo Cao¹, Yongchang Tang², Feng Yuan³, Gaoyuan Yang¹, Zhiwei He¹, Zheng Shi¹, Xiaorui Su¹, Zhicheng Yao⁴, Meihai Deng¹

Affiliations

¹ Department of Hepatobiliary Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
² Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China.
³ Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
⁴ Department of Hepatobiliary and Pancreatic Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

PMID: 38751440
PMCID: PMC11090797
DOI: 10.21147/j.issn.1000-9604.2024.02.02

Abstract

Objective: Unresectable hepatocellular carcinoma (uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization (TACE) for the treatment of uHCC.

Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival (PFS), objective response rate (ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while survival analysis was conducted through Kaplan-Meier curve analysis for overall survival (OS) and PFS. Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).

Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval (95% CI), 5.3-14.6] months, and the median PFS (mPFS) was 15.5 (95% CI, 5.4-NA) months. Median OS (mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate (DCR) was 70.6%. AEs were reported in 27 (79.4%) patients. The most frequently reported AEs (with an incidence rate >10%) included abnormal liver function (52.9%), abdominal pain (44.1%), abdominal distension and constipation (29.4%), hypertension (20.6%), leukopenia (17.6%), constipation (17.6%), ascites (14.7%), and insomnia (14.7%). Abnormal liver function (14.7%) had the most common grade 3 or higher AEs.

Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for uHCC, showcasing a promising therapeutic strategy for managing uHCC.

Keywords: Hepatocellular carcinoma; lenvatinib; low-dose cyclophosphamide; pembrolizumab; transarterial chemoembolization.