PMID- 38196523 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240227 IS - 2078-6891 (Print) IS - 2219-679X (Electronic) IS - 2078-6891 (Linking) VI - 14 IP - 6 DP - 2023 Dec 31 TI - Efficacy and safety of regorafenib in combination with immune checkpoint inhibitor therapy as second-line and third-line regimen for patients with advanced hepatocellular carcinoma: a retrospective study. PG - 2549-2558 LID - 10.21037/jgo-23-590 [doi] AB - BACKGROUND: Despite the emergence of immune checkpoint inhibitors (ICIs) as first-line treatment for advanced hepatocellular carcinoma (HCC), there is an unmet need regarding subsequent treatments in patients that fail ICI. Regorafenib is a vascular endothelial growth factor receptor (VEGFR) inhibitor, which could increase programmed death-ligand 1 (PD-L1) expression in tumors and increase intra-tumoral CD8(+) T-cell infiltration by normalizing the cancer vasculature and improving the efficacy of the programmed cell death protein 1 (PD-1) antibody. Thus, we evaluated the combination of regorafenib and a PD-1 inhibitor for advanced HCC patients that had failed combined tyrosine kinase inhibitors (TKIs) plus ICI. METHODS: Data of patients with advanced HCC who had failed combined TKIs plus ICI treatment and were afterwards treated with combined regorafenib plus a PD-1 inhibitor were reviewed. All patients had received PD-1 inhibitors as part of the first-line treatment and regorafenib every 4 weeks until disease progression, intolerable toxicities, or physician/patient withdrawal. The clinical data, previous treatment strategies, follow-up imaging results, and adverse events (AEs) during follow-ups were recorded. Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 was used to evaluate AEs and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 was used to evaluate response. The primary endpoint was safety, and the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and duration of response (DOR). RESULTS: From November 15, 2020, to January 31, 2022, data of 17 patients with advanced HCC that met the criteria were reviewed. The cohort included 16 men and 1 woman with a median age of 54 years (interquartile range, 46 to 63 years). Sixteen patients had Child-Pugh class A (n=16, 94.12%) and one with class B (n=1, 15.9%) liver disease. Thirteen patients received second-line treatment, and the remaining patients received third-line treatment. All patients received at least 1 dose of PD-1 inhibitors. The median follow-up duration was 7.62 months. Twelve recipients experienced treatment-related AEs. The most frequent AE (>/=5%) included fatigue (17.64%), diarrhea (17.65%), proteinuria (5.88%), bleeding gums (11.76%), and hypertension (11.76%). No grade-4 AE or new safety signals were identified. The ORR and DCR were 41.2% and 64.7%, respectively, and the median PFS was 5.09 months. CONCLUSIONS: Regorafenib combined with PD-1 inhibitor is a promising regimen in treating patients with advanced HCC owing to its safety and effectiveness as well as low incidence of serious AEs with its use. CI - 2023 Journal of Gastrointestinal Oncology. All rights reserved. FAU - Zhao, Jie AU - Zhao J AD - Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China. FAU - Guo, Yongzhong AU - Guo Y AD - Department of General Surgery, Ili & Jiangsu Joint Institute of Health, Ili, China. FAU - Feng, Tianshuo AU - Feng T AD - Nanjing Medical University, Nanjing, China. FAU - Rong, Dawei AU - Rong D AD - Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China. FAU - Kong, Xiangyi AU - Kong X AD - Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China. FAU - Huang, Tian AU - Huang T AD - Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China. FAU - Lopez-Lopez, Victor AU - Lopez-Lopez V AD - Department of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain. FAU - Yarmohammadi, Hooman AU - Yarmohammadi H AD - Division of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Sakamoto, Yoshihiro AU - Sakamoto Y AD - Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan. FAU - Zhu, Deming AU - Zhu D AD - Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China. FAU - Yao, Aihua AU - Yao A AD - Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China. FAU - Xia, Yongxiang AU - Xia Y AD - Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20231227 PL - China TA - J Gastrointest Oncol JT - Journal of gastrointestinal oncology JID - 101557751 PMC - PMC10772671 OTO - NOTNLM OT - Immune checkpoint inhibitors (ICIs) OT - advanced hepatocellular carcinoma (advanced HCC) OT - immune resistance OT - regorafenib OT - second-line treatment COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-590/coif). The authors have no conflicts of interest to declare. EDAT- 2024/01/10 06:41 MHDA- 2024/01/10 06:42 PMCR- 2023/12/31 CRDT- 2024/01/10 03:36 PHST- 2023/07/17 00:00 [received] PHST- 2023/12/13 00:00 [accepted] PHST- 2024/01/10 06:42 [medline] PHST- 2024/01/10 06:41 [pubmed] PHST- 2024/01/10 03:36 [entrez] PHST- 2023/12/31 00:00 [pmc-release] AID - jgo-14-06-2549 [pii] AID - 10.21037/jgo-23-590 [doi] PST - ppublish SO - J Gastrointest Oncol. 2023 Dec 31;14(6):2549-2558. doi: 10.21037/jgo-23-590. Epub 2023 Dec 27.