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

San Chi Chen, Yi Hsiang Huang, Ming Huang Chen, Yi Ping Hung, Rheun Chuan Lee, Yu Yun Shao, Yee Chao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number55
JournalBMC Cancer
Volume22
Issue number1
DOIs
StatePublished - Dec 2022

Keywords

  • Anti-PD-1
  • Combination therapy
  • Hepatocellular carcinoma (HCC)
  • Multiple-kinase inhibitor
  • Nivolumab
  • Pembrolizumab
  • Propensity score matching (PSM)
  • Sorafenib
  • Vascular endothelial growth factor (VEGF)

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