Anti-PD-1 combined sorafenib versus anti-PD-1 alone in the treatment of advanced hepatocellular cell carcinoma: a propensity score-matching study

• Published in: BMC cancer Vol. 22; no. 1; p. 55
• Main Authors: Chen, San-Chi, Huang, Yi-Hsiang, Chen, Ming-Huang, Hung, Yi-Ping, Lee, Rheun-Chuan, Shao, Yu-Yun, Chao, Yee
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.01.2022; BioMed Central; BMC
• Subjects: Adrenal glands; Aged; Aged, 80 and over; Analysis; Anti-PD-1; Antineoplastic Agents - therapeutic use; Biomarkers; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Care and treatment; Diagnosis; Disease; Drug Therapy, Combination; Female; Hepatitis; Hepatocellular carcinoma; Hepatocellular carcinoma (HCC); Hepatoma; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunomodulation; Liver; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Male; Medical prognosis; Medical research; Metastases; Metastasis; Middle Aged; Multiple-kinase inhibitor; Nivolumab; Patient outcomes; Patients; PD-1 protein; Pembrolizumab; Peritoneum; Prevention; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Propensity Score; Retrospective Studies; Risk factors; Sorafenib; Sorafenib - therapeutic use; Statistical analysis; Targeted cancer therapy; Thrombosis; Tumor microenvironment; Tumors; Vascular endothelial growth factor; Taiwan; Pembrolizumab; Anti-PD-1; Nivolumab; Sorafenib; Vascular endothelial growth factor (VEGF); Hepatocellular carcinoma (HCC); Combination therapy; Propensity score matching (PSM); Multiple-kinase inhibitor
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09173-4

Vascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC). HCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching. There were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28. This is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.