Scholarlink

<p>Conversion therapy remains an uncommon strategy for managing unresectable hepatocellular carcinoma (uHCC) due to limited evidence supporting its efficacy. To address this gap, we initiated a prospective phase 2 multicenter trial (NCT04997850) comparing the LEN-TAP regimen, combining lenvatinib, transarterial chemoembolization (TACE), and PD-1 inhibitors, against TACE alone in uHCC patients. The study’s primary outcome was salvage liver resection (SLR) rate; secondary measures included objective response rate (ORR), overall survival (OS), event-free survival (EFS), recurrence-free survival (RFS), and safety profile. From October 2020 to November 2021, 142 eligible participants were assigned to LEN-TAP (n = 71) or TACE monotherapy (n = 71). At a median follow-up of 24.2 months, the LEN-TAP cohort exhibited a significantly higher SLR rate (59.2% vs. 18.3%, P &lt; 0.001) and ORR (78.9% vs. 16.9%, P &lt; 0.001). Median OS, EFS, and RFS were also substantially prolonged in the LEN-TAP cohort (not reached vs. 23.0 months, P &lt; 0.001; 20.03 vs. 6.52 months, P &lt; 0.001; 36.6 vs. 19.0 months, P = 0.048). Although grade 3 treatment-related AEs occurred more frequently with LEN-TAP (60.6% vs. 21.1%, P &lt; 0.001), no grade 4 or higher toxicities were observed. Exploratory biomarker assessments via single-cell sequencing and flow cytometry linked elevated levels of circulating HLA-DR<sup>+</sup>CD38<sup>+</sup>CD8<sup>+</sup> T cells with improved treatment response. These T cells appear to mediate antitumor activity potentially through the CXCR6–PI3K–AKT signaling axis. In summary, the LEN-TAP protocol demonstrates promising efficacy and acceptable tolerability as a conversion therapy in uHCC, with peripheral HLA-DR<sup>+</sup>CD38<sup>+</sup>CD8<sup>+</sup> T cell abundance serving as a potential predictor of therapeutic benefit.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月22日

查看全文
  • Xiaoyun Zhang,
  • Haozheng Cai,
  • Wei Peng,
  • Haiqing Wang,
  • JiaYi Wu,
  • Xinrui Zhu,
  • Weixin Guo,
  • Fei Xie,
  • Yu Zhang,
  • Ming Wang,
  • Yu Yu,
  • Yongjie Zhou,
  • Chuan Li,
  • Junyi Shen,
  • Chang Liu,
  • Yu Yang,
  • Xiaozhong Jiang,
  • Qiu Li,
  • Weixia Chen,
  • Yujun Shi,
  • Wusheng Lu,
  • Xin Sun,
  • Xielin Feng,
  • Maolin Yan,
  • Shuqun Cheng,
  • Tianfu Wen

摘要

Conversion therapy remains an uncommon strategy for managing unresectable hepatocellular carcinoma (uHCC) due to limited evidence supporting its efficacy. To address this gap, we initiated a prospective phase 2 multicenter trial (NCT04997850) comparing the LEN-TAP regimen, combining lenvatinib, transarterial chemoembolization (TACE), and PD-1 inhibitors, against TACE alone in uHCC patients. The study’s primary outcome was salvage liver resection (SLR) rate; secondary measures included objective response rate (ORR), overall survival (OS), event-free survival (EFS), recurrence-free survival (RFS), and safety profile. From October 2020 to November 2021, 142 eligible participants were assigned to LEN-TAP (n = 71) or TACE monotherapy (n = 71). At a median follow-up of 24.2 months, the LEN-TAP cohort exhibited a significantly higher SLR rate (59.2% vs. 18.3%, P < 0.001) and ORR (78.9% vs. 16.9%, P < 0.001). Median OS, EFS, and RFS were also substantially prolonged in the LEN-TAP cohort (not reached vs. 23.0 months, P < 0.001; 20.03 vs. 6.52 months, P < 0.001; 36.6 vs. 19.0 months, P = 0.048). Although grade 3 treatment-related AEs occurred more frequently with LEN-TAP (60.6% vs. 21.1%, P < 0.001), no grade 4 or higher toxicities were observed. Exploratory biomarker assessments via single-cell sequencing and flow cytometry linked elevated levels of circulating HLA-DR+CD38+CD8+ T cells with improved treatment response. These T cells appear to mediate antitumor activity potentially through the CXCR6–PI3K–AKT signaling axis. In summary, the LEN-TAP protocol demonstrates promising efficacy and acceptable tolerability as a conversion therapy in uHCC, with peripheral HLA-DR+CD38+CD8+ T cell abundance serving as a potential predictor of therapeutic benefit.