Efficacy and Safety of Regorafenib with or without PD-1 Inhibitors as Second-Line Therapy for Advanced Hepatocellular Carcinoma in Real-World Clinical Practice

Kan Liu; Jianbing Wu; Yongkang Xu; Dan Li; Shenlang Huang; Ye Mao

doi:10.2147/OTT.S383685

Efficacy and Safety of Regorafenib with or without PD-1 Inhibitors as Second-Line Therapy for Advanced Hepatocellular Carcinoma in Real-World Clinical Practice

Onco Targets Ther. 2022 Oct 1:15:1079-1094. doi: 10.2147/OTT.S383685. eCollection 2022.

Authors

Kan Liu^#^{1

2}, Jianbing Wu^#^{1

2}, Yongkang Xu^{1

2}, Dan Li^{1

2}, Shenlang Huang^{1

2}, Ye Mao^{1

2}

Affiliations

¹ Department of Digestive Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
² Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, People's Republic of China.

^# Contributed equally.

Abstract

Background: Regorafenib is the first oral targeted drug as a second-line agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib treatment. Recently, several studies demonstrated that the combination of regorafenib and PD-1 inhibitors showed a synergistic effect. Our study aimed to evaluate the efficacy of regorafenib with PD-1 inhibitors (RP) and regorafenib alone (R) as second-line treatment for advanced HCC.

Methods: From October 2018 to January 2022, our retrospective study evaluated advanced HCC patients who received regorafenib with PD-1 inhibitors or regorafenib alone as a second-line treatment at the Second Affiliated Hospital of Nanchang University, China. The efficacy and safety were compared between RP and R groups.

Results: In total, 78 patients were enrolled in our study and were separated into two groups - RP group (48) and R group (30) - according to the criteria. The ORR of RP group and R group was 18.8% and 10%, respectively, and the DCR was 66.7% and 43.3%, respectively. The RP group had a longer mPFS (5.9 months vs 3.0 months, P<0.001) and mOS (12.9 months vs 10.3 months, P=0.010) than the R group. Regorafenib monotherapy is an independent prognostic factor for OS and PFS. In OS, subgroup analysis showed that patients with AFP ≥ 400ng/mL, BCLC C stage and extrahepatic metastasis may benefit from RP, while in PFS, subgroup analysis showed that patients with BCLC C stage, AFP ≥ 400ng/mL, extrahepatic metastasis, ALBI ≥-2.60 and first-line treatment of sorafenib may benefit from RP. The incidence of grade 3/4 adverse reaction in the two groups was 22.9% and 23.3%, respectively, with no significant statistically difference (P=0.966).

Conclusion: In the second-line therapy of advanced HCC, compared to regorafenib alone, the combination of regorafenib and PD-1 inhibitors showed promising efficacy and tolerable drug toxicity.

Keywords: PD-1 inhibitor; hepatocellular carcinoma; immunotherapy; regorafenib; second-line therapy.

Grants and funding

This study was supported by National Natural Science Foundation of China (No. 82160602) and Youth Project of science and Technology Research Project of Jiangxi Education Department (No. GJJ200251).