Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
BMC Cancer. 2022 Jan 11;22(1):55. 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.
血管内皮生长因子（VEGF）在肿瘤微环境中发挥作用。索拉非尼可抑制 VEGF 通路，具有免疫调节功能，但缺乏大量的临床数据。本研究旨在探讨抗 PD-1 联合索拉非尼治疗晚期肝细胞癌（HCC）的疗效。
回顾性分析 2016 年 1 月至 2019 年 2 月在台北荣民总医院接受抗 PD-1 治疗的 HCC 患者。采用倾向评分匹配比较两组患者的疗效。
共纳入 173 例 HCC 患者，排除不适合病例后，对 140 例患者进行了分析，其中 58 例接受联合治疗，82 例接受抗 PD-1 单药治疗。联合治疗组的 CR 率（8.6% vs. 4.9%，ns.）、ORR（22.4% vs. 19.5%，ns.）较高，DCR（69.0% vs. 37.8%，p<0.05）显著高于抗 PD-1 单药组。匹配后，联合组的无进展生存期（3.87 个月 vs. 2.43 个月，p<0.05）和总生存期（未达到 vs. 7.17 个月，p<0.05）均长于抗 PD-1 单药组，且 3/4 级 AE 发生率（10.3% vs. 7.1%，p=0.73）无差异。不同转移部位的肿瘤反应不同，肾上腺、腹膜和肺部的反应较高。AFP 下降幅度越大（>10%、>50%和>66%），第 28 天的 ORR（70%、80%和 92%）和 CR 率（30%、35%和 58%）越高。
本研究首次证明抗 PD-1 联合索拉非尼治疗具有更好的疗效和生存获益。需要前瞻性随机研究来证实这一发现。
