Scholarlink

Purpose <p>Anti-PD-1 immune-checkpoint inhibitors (ICIs) are approved for treating patients with recurrent or metastatic (R/M) esophageal squamous cell carcinoma (ESCC) who have failed platinum-based chemotherapy. However, their efficacy as monotherapy remains limited. We hypothesized that adding cabozantinib, a multikinase inhibitor with antiangiogenic and immunomodulatory properties, could enhance the therapeutic efficacy of atezolizumab, an anti-PD-L1 ICI, in patients with R/M ESCC.</p> Patients and methods <p>A single-arm, single-institution phase II trial was conducted (NCT05007613) that included patients with ESCC who experienced disease progression following a platinum-based chemotherapy for R/M ESCC or within 6&#xa0;months after chemo(radio)therapy for locoregional disease. Participants received cabozantinib 40&#xa0;mg daily and atezolizumab 1200&#xa0;mg every 3&#xa0;weeks until disease progression or intolerable toxicity was reached. The primary endpoint was investigator-assessed objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile.</p> Results <p>Between June 2021 and March 2024, 24 patients were enrolled in this study. With a median follow-up of 7.0&#xa0;months (range, 0.5–38.1), 7 patients achieved partial responses and 7 had stable disease. The ORR was 29.1% (95% CI = 11.7%-60.1%), and the disease control rate (DCR) was 58.3% (95% CI = 31.9–97.9%). The median duration of response was 6.5&#xa0;months (95% CI = 0.9–12.1), the median PFS was 2.2&#xa0;months (95% CI = 0.64–3.76), and the median OS was 7&#xa0;months (95% CI = 2.36–11.64). Of the 24 patients, 12 (50%) experienced ≥ grade 3 treatment-related adverse events. Patients with high PD-L1 expression and increased intratumoral or stromal CD8+ tumor infiltrating lymphocytes had numerically higher ORR and improved OS.</p> Conclusion <p>The combination of cabozantinib and atezolizumab has an acceptable safety profile and moderate antitumor activity as a second-line treatment for patients with R/M ESCC.</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

Cabozantinib and atezolizumab for recurrent or metastatic esophageal squamous cell carcinoma after platinum-based chemotherapy failure: a single-arm phase II study and biomarker analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月9日

查看全文
  • Hung-Yang Kuo,
  • Ta-Chen Huang,
  • Chien-Huai Chuang,
  • Tsung-Che Wu,
  • Yen-Lin Huang,
  • Chia-Chi Lin,
  • Jang-Ming Lee,
  • Jhe-Cyuan Guo,
  • Chih-Hung Hsu

摘要

Purpose

Anti-PD-1 immune-checkpoint inhibitors (ICIs) are approved for treating patients with recurrent or metastatic (R/M) esophageal squamous cell carcinoma (ESCC) who have failed platinum-based chemotherapy. However, their efficacy as monotherapy remains limited. We hypothesized that adding cabozantinib, a multikinase inhibitor with antiangiogenic and immunomodulatory properties, could enhance the therapeutic efficacy of atezolizumab, an anti-PD-L1 ICI, in patients with R/M ESCC.

Patients and methods

A single-arm, single-institution phase II trial was conducted (NCT05007613) that included patients with ESCC who experienced disease progression following a platinum-based chemotherapy for R/M ESCC or within 6 months after chemo(radio)therapy for locoregional disease. Participants received cabozantinib 40 mg daily and atezolizumab 1200 mg every 3 weeks until disease progression or intolerable toxicity was reached. The primary endpoint was investigator-assessed objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile.

Results

Between June 2021 and March 2024, 24 patients were enrolled in this study. With a median follow-up of 7.0 months (range, 0.5–38.1), 7 patients achieved partial responses and 7 had stable disease. The ORR was 29.1% (95% CI = 11.7%-60.1%), and the disease control rate (DCR) was 58.3% (95% CI = 31.9–97.9%). The median duration of response was 6.5 months (95% CI = 0.9–12.1), the median PFS was 2.2 months (95% CI = 0.64–3.76), and the median OS was 7 months (95% CI = 2.36–11.64). Of the 24 patients, 12 (50%) experienced ≥ grade 3 treatment-related adverse events. Patients with high PD-L1 expression and increased intratumoral or stromal CD8+ tumor infiltrating lymphocytes had numerically higher ORR and improved OS.

Conclusion

The combination of cabozantinib and atezolizumab has an acceptable safety profile and moderate antitumor activity as a second-line treatment for patients with R/M ESCC.