A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma

Tao Yan; Chenyang Huang; Caiyun Peng; Xuezhang Duan; Dong Ji; Youjia Duan; Wen Zhang; Haitao Zhao; Kun Gao; Xiangyu Yang; Linzhi Zhang; Jiamin Cheng; Tiago Biachi de Castria; Christine Pocha; Diamantis I Tsilimigras; Tong Wu; Guodong Su; Yinyin Li; Lingxiang Yu; Yinying Lu

doi:10.21037/atm-22-6614

A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma

Ann Transl Med. 2023 Jan 31;11(2):109. doi: 10.21037/atm-22-6614.

Authors

Tao Yan^#¹, Chenyang Huang^#¹, Caiyun Peng^#¹, Xuezhang Duan¹, Dong Ji¹, Youjia Duan², Wen Zhang³, Haitao Zhao⁴, Kun Gao⁵, Xiangyu Yang⁵, Linzhi Zhang¹, Jiamin Cheng¹, Tiago Biachi de Castria⁶, Christine Pocha⁷, Diamantis I Tsilimigras⁸, Tong Wu¹, Guodong Su¹, Yinyin Li¹, Lingxiang Yu¹, Yinying Lu¹

Affiliations

¹ Comprehensive HCC Center, The Fifth Medical Center of the PLA General Hospital, Beijing, China.
² Department of Tumor Intervention, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
³ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Department of Liver Surgery, Peking Union Medical College Hospital, Beijing, China.
⁵ Department of Intervention Therapy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
⁶ Moffitt Cancer Center, Tampa, FL, USA.
⁷ Avera Hepatology and Transplant Institute, University of South Dakota, Sioux Falls, SD, USA.
⁸ Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.

^# Contributed equally.

Abstract

Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the combination therapy of regorafenib and programmed death-1 (PD-1) inhibitors with regorafenib monotherapy as a second-line treatment for patients with advanced HCC.

Methods: Our multicenter retrospective study evaluated consecutive patients with advanced HCC who received regorafenib plus PD-1 inhibitors or regorafenib alone as a later-line therapy from May 2019 to January 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and safety was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Results: A total of 133 patients were included in the study (regardless of first-line treatment), including 94 who received regorafenib plus PD-1 inhibitors and 39 who received regorafenib. The regorafenib plus PD-1 inhibitors group had a significantly higher ORR (25.53% vs. 10.26%, P=0.015), higher DCR (87.23% vs. 66.67%, P=0.006), and longer PFS (median 9.0 vs. 4.0 months, P<0.0001) than the regorafenib group. Meanwhile, the median OS (mOS) did not differ between the regorafenib plus PD-1 and regorafenib monotherapy groups {mOS, 14.0 months [95% confidence interval (CI), 14.0-16.0 months] vs. 12.0 months (95% CI, 10.0-22.0 months)}. There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (71.79% vs. 78.72%, P=0.39) and the incidence of grade 3/4 serious adverse effects (5.13% vs. 18.09%, P=0.19) between the regorafenib monotherapy group and PD-1 inhibitors combination group.

Conclusions: Compared with regorafenib alone, regorafenib combined with PD-1 inhibitors therapy increased PFS, ORR but did not improve OS, and can be used an option in second-line HCC therapy, regardless of first-line treatments. Regorafenib combined with PD-1 inhibitors is recommended as early as a second-line therapy to benefit patients. The combination regimen was as safe as regorafenib monotherapy for treatment of HCC in patients with compensated liver disease [Child-Turcotte-Pugh (CTP) A/B].

Keywords: Efficacy; hepatocellular carcinoma (HCC); regorafenib; safety.