Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia.
Winship Cancer Institute of Emory University, Atlanta, Georgia.
Clin Cancer Res. 2024 Oct 15;30(20):4601-4608. doi: 10.1158/1078-0432.CCR-24-1202.
Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) have immunomodulatory properties and improve clinical outcomes in combination with anti-PD-1 therapy in different malignancies. We report the long-term efficacy and safety of pembrolizumab and cabozantinib in patients with RMHNSCC and include a correlative biomarker analysis.
This open-label, single-arm, multicenter, phase 2 study screened 50 patients with RMHNSCC, of whom 36 received pembrolizumab and cabozantinib. The primary endpoint was overall response rate (ORR), safety, and tolerability. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and correlative studies of tissue and blood. We report the long-term PFS, OS, and safety of treated patients and describe correlative biomarkers evaluating p-MET expression and tumor immune microenvironment (TIME) using multiplex immunohistochemistry.
With median follow-up of 22.4 months, the median PFS was 12.8 months with a 2-year PFS of 32.6% (95% CI, 18.8%-56.3%) and the median OS was 27.7 months with a 2-year OS of 54.7% [95% confidence interval (CI), 38.9%-76.8%]. The median duration of response was 12.6 months with a 2-year rate of 38.5% (95% CI, 30.8%-81.8%). Long-term treatment-related adverse events included manageable hypothyroidism (5.5%) and grade 1 elevated aspartate aminotransferase and alanine aminotransferase (2.8%). Baseline tumor p-MET expression correlated with ORR (P = 0.0055). Higher density of CD8+, CD103+, and CSF1-R+ cells at baseline correlated with improved OS [hazard ratio (HR) = 5.27, P = 0.030; HR = 8.79, P = 0.017; HR = 6.87, P = 0.040, respectively].
Pembrolizumab and cabozantinib provided prolonged encouraging long-term disease control and survival with a maintained favorable safety profile. The prognostic significance of higher density of CD8+, CD103+, and CSF1-R+ cells in TIME deserve further evaluation in similar clinical settings.
抗程序性细胞死亡蛋白 1（PD-1）治疗是复发性和/或转移性头颈部鳞状细胞癌（RMHNSCC）的标准治疗方法。血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKI）具有免疫调节特性，并在不同恶性肿瘤中与抗 PD-1 治疗联合使用可改善临床结局。我们报告了 pembrolizumab 和 cabozantinib 治疗 RMHNSCC 患者的长期疗效和安全性，并进行了相关的生物标志物分析。
这是一项开放标签、单臂、多中心、2 期研究，共筛选了 50 例 RMHNSCC 患者，其中 36 例接受 pembrolizumab 和 cabozantinib 治疗。主要终点为总缓解率（ORR）、安全性和耐受性。次要终点包括无进展生存期（PFS）、总生存期（OS）和组织及血液的相关性研究。我们报告了接受治疗患者的长期 PFS、OS 和安全性，并描述了使用多重免疫组化评估组织中 p-MET 表达和肿瘤免疫微环境（TIME）的相关生物标志物。
中位随访 22.4 个月时，中位 PFS 为 12.8 个月，2 年 PFS 为 32.6%（95%CI，18.8%-56.3%），中位 OS 为 27.7 个月，2 年 OS 为 54.7%[95%置信区间（CI），38.9%-76.8%]。中位缓解持续时间为 12.6 个月，2 年缓解率为 38.5%（95%CI，30.8%-81.8%）。长期治疗相关不良事件包括可管理的甲状腺功能减退症（5.5%）和 1 级天门冬氨酸氨基转移酶和丙氨酸氨基转移酶升高（2.8%）。基线肿瘤 p-MET 表达与 ORR 相关（P=0.0055）。基线时 CD8+、CD103+和 CSF1-R+细胞密度较高与 OS 改善相关[风险比（HR）=5.27，P=0.030；HR=8.79，P=0.017；HR=6.87，P=0.040]。
pembrolizumab 和 cabozantinib 提供了持久的令人鼓舞的长期疾病控制和生存，且保持了良好的安全性。TIME 中 CD8+、CD103+和 CSF1-R+细胞密度较高的预后意义值得在类似临床环境中进一步评估。
