卡博替尼联合阿替利珠单抗用于铂类化疗失败后复发或转移性食管鳞状细胞癌：单臂 II 期研究及生物标志物分析

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.

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.

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.

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.