Adjuvant Lenvatinib Plus PD-1 Antibody for Hepatocellular Carcinoma with High Recurrence Risks After Hepatectomy: A Retrospective Landmark Analysis

Jingzhong Ouyang; Zhengzheng Wang; Kun Yuan; Yi Yang; Yanzhao Zhou; Qingjun Li; Nanmu Yang; Haitao Zhao; Hong Zhao; Jinxue Zhou

doi:10.2147/JHC.S424616

Adjuvant Lenvatinib Plus PD-1 Antibody for Hepatocellular Carcinoma with High Recurrence Risks After Hepatectomy: A Retrospective Landmark Analysis

J Hepatocell Carcinoma. 2023 Sep 6:10:1465-1477. doi: 10.2147/JHC.S424616. eCollection 2023.

Authors

Jingzhong Ouyang^#¹, Zhengzheng Wang^#¹, Kun Yuan^#², Yi Yang^{3

4}, Yanzhao Zhou¹, Qingjun Li¹, Nanmu Yang¹, Haitao Zhao⁵, Hong Zhao^{3

4}, Jinxue Zhou¹

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China.
² School of Public Health, Capital Medical University, Beijing, People's Republic of China.
³ Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
⁴ Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
⁵ Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: To evaluate the efficacy and safety of lenvatinib plus programmed death-1 (PD-1) antibody as postoperative adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risks of recurrence.

Patients and methods: A series of 137 patients with HCC at high risks of recurrence who underwent hepatectomy at our hospital between October 2019 and January 2022 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Landmark analysis was used to compare short- and long-term RFS. Univariable and multivariable analyses were used to identify prognostic factors, and subgroup analyses were performed according to high risks of recurrence.

Results: A total of 85 patients underwent hepatectomy alone and 52 patients received postoperative adjuvant therapy. Compared with the hepatectomy group (HG), RFS was significantly improved in the adjuvant therapy group (ATG) (P < 0.001), but OS was not (P = 0.098). Landmark analysis revealed that RFS within 6 months of the HG was significantly different from that of the ATG (P < 0.001) but not after 6 months (P = 0.486). Multivariable analysis showed that without adjuvant therapy, high Child-Pugh classification, high alpha-fetoprotein levels, microvascular invasion, and satellite lesions were independent risk factors for recurrence within 6 months after hepatectomy. Subgroup analysis revealed that patients with MVI significantly benefited from adjuvant therapy in RFS. But for OS, adjuvant therapy was only significantly effective in patients with single tumor. The most common treatment-related adverse events during adjuvant therapy were hypertension (36.5%), rash or itching (28.8%), diarrhea (23.1%), and fatigue (21.2%).

Conclusion: Postoperative adjuvant lenvatinib plus PD-1 antibody significantly improved RFS in patients with HCC at high risks of recurrence with acceptable safeties.

Keywords: PD-1 antibody; efficacy; hepatocellular carcinoma; lenvatinib; postoperative adjuvant therapy; safety.

Grants and funding

This work was sponsored by the Henan Provincial Medical Science and Technology Research Project (LLRGJ20220191), Key Scientific Research Project of Colleges and Universities in Henan Province (23A320033), Henan Provincial Science and Technology Project (232102311080), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-12M-C&T-B-081), Special Research Fund for Central Universities, Peking Union Medical College (No. 3332022026), and Youth Project of Beijing Hope Marothon Special Fund (No. LC2021B17), the National Natural Science Foundation of China (No. 81972311, No. 82141127), the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2021-I2M-1-066), and the Non-profit Central Research Institution Fund of the Chinese Academy of Medical Sciences (No. 2019PT310026).