Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma

Yan-Yu Wang, Xu Yang, Yun-Chao Wang, Jun-Yu Long, Hui-Shan Sun, Yi-Ran Li, Zi-Yu Xun, Nan Zhang, Jing-Nan Xue, Cong Ning, Jun-Wei Zhang, Cheng-Pei Zhu, Long-Hao Zhang, Xiao-Bo Yang, Hai-Tao Zhao, Yan-Yu Wang, Xu Yang, Yun-Chao Wang, Jun-Yu Long, Hui-Shan Sun, Yi-Ran Li, Zi-Yu Xun, Nan Zhang, Jing-Nan Xue, Cong Ning, Jun-Wei Zhang, Cheng-Pei Zhu, Long-Hao Zhang, Xiao-Bo Yang, Hai-Tao Zhao

Abstract

Background: Programmed death receptor-1 (PD-1) inhibitors have been approved as second-line treatment regimen in hepatocellular carcinoma (HCC), but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.

Aim: To estimate the clinical outcome of transarterial chemoembolization (TACE) and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC (uHCC).

Methods: We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022. 45 patients received the PD-1 inhibitors, lenvatinib, TACE (PD-1-Lenv-T) therapy, and 20 received the lenvatinib, TACE (Lenv-T) therapy. In terms of the dose of lenvatinib, 8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg. Of the patients in the PD-1 inhibitor combination group, 15 received Toripalimab, 14 received Toripalimab, 14 received Camrelizumab, 4 received Pembrolizumab, 9 received Sintilimab, and 2 received Nivolumab, 1 with Tislelizumab. According to the investigators' assessment, TACE was performed every 4-6 wk when the patient had good hepatic function (Child-Pugh class A or B) until disease progression occurred. We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors (mRECIST criteria). We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0. The key adverse events (AEs) after the initiation of combination therapy were observed.

Results: Patients with uHCC who received PD-1-Lenv-T therapy (n = 45) had a clearly longer overall survival than those who underwent Lenv-T therapy (n = 20, 26.8 vs 14.0 mo; P = 0.027). The median progression-free survival time between the two treatment regimens was also measured {11.7 mo [95% confidence interval (CI): 7.7-15.7] in the PD-1-Lenv-T group vs 8.5 mo (95%CI: 3.0-13.9) in the Lenv-T group (P = 0.028)}. The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4% and 20% (P = 0.059) according to the mRECIST criteria, meanwhile the disease control rates were 93.3% and 64.0% (P = 0.003), respectively. The type and frequency of AEs showed little distinction between patients received the two treatment regimens.

Conclusion: Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.

Keywords: Combination therapy; Hepatocellular carcinoma; Immunotherapy; Lenvatinib; Programmed death receptor-1 inhibitor; Transarterial chemoembolization.

Conflict of interest statement

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

Figures

Figure 1
Figure 1
Workflow of this study. TACE: Transarterial chemoembolization; PD-1: Programmed death receptor-1.
Figure 2
Figure 2
The overall survival and progression-free survival times of all included patients and programmed death receptor-1-lenvatinib-transarterial chemoembolization group and lenvatinib-transarterial chemoembolization group. A: The overall survival (OS) times of all included patients; B: The progression-free survival (PFS) times of all included patients; C: The OS times of programmed death receptor-1 (PD-1)-lenvatinib-transarterial chemoembolization (TACE) group and lenvatinib-TACE group; D: The PFS times of PD-1-lenvatinib-TACE group and lenvatinib-TACE group. OS: Overall survival; PFS: Progression-free survival; CI: Confidence interval; PD-1: Programmed death receptor-1.
Figure 3
Figure 3
Univariate and multivariable Cox regression analysis for overall survival and progression-free survival. A: Univariate Cox regression analysis for overall survival (OS); B: Multivariable Cox regression analysis for OS; C: Univariate Cox regression analysis for progression-free survival (PFS); D: Multivariable Cox regression analysis for PFS. aP < 0.05. HR: Hazard ratio; CI: Confidence interval; PD-1: Programmed death receptor-1; TACE: Transarterial chemoembolization; ECOG-PS: Eastern Cooperative Oncology Group performance status; BCLC: Barcelona Clinic Liver Cancer; AFP: Alpha-fetoprotein; TBS: Tumor burden score.

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