Pembrolizumab and Cabozantinib in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Long-term Survival Update with a Biomarker Analysis.

IF 10 1区 医学 Q1 ONCOLOGY
Nabil F Saba, Ritu Chaudhary, Kedar Kirtane, Angelo Marra, Asari Ekpenyong, Ashley McCook-Veal, Nicole C Schmitt, Jennifer H Gross, Mihir R Patel, Jill Remick, James E Bates, Mark W McDonald, Soumon F Rudra, William A Stokes, Maria Biernacki, Xiaofei Song, Robbert J C Slebos, Yuan Liu, Conor E Steuer, Dong M Shin, Yong Teng, Christine H Chung
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引用次数: 0

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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].

Conclusions: 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.

Pembrolizumab和cabozantinib治疗复发性和/或转移性头颈部鳞状细胞癌(RMHNSCC):通过生物标记分析更新长期生存率。
目的:抗程序性细胞死亡蛋白1(PD-1)疗法是治疗复发性和/或转移性头颈部鳞状细胞癌(RMHNSCC)的标准疗法。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,与抗PD-1疗法联合使用可改善临床疗效。我们报告了pembrolizumab和cabozantinib的长期疗效和安全性,并进行了相关生物标记物分析:这项开放标签、单臂、多中心、2 期研究筛选了 50 名 RMHNSCC 患者,其中 36 人接受了 pembrolizumab 和 cabozantinib 治疗。主要终点是总反应率(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)以及组织和血液的相关研究。我们报告了长期无进展生存期(PFS)、总生存期(OS)、安全性,并描述了相关生物标志物:中位随访时间为22.4个月,中位PFS为12.8个月,2年PFS为32.6%(95%CI为18.8-56.3%),中位OS为27.7个月,2年OS为54.7%(95%CI为38.9-76.8%)。中位应答持续时间为12.6个月,2年应答率为38.5%(95%CI 30.8-81.8%)。长期TRAE包括可控制的甲状腺功能减退(5.5%)和1级AST和ALT升高(2.8%)。基线肿瘤 p-MET 表达与 ORR 相关(p=0.0055)。基线CD8+、CD103+和CSF1-R+细胞密度较高与OS改善相关(危险比[HR]分别为5.27,p=0.030;HR=8.79,p=0.017;HR=6.87,p=0.040):结论:Pembrolizumab和卡博替尼能延长令人鼓舞的长期疾病控制和生存期,并保持良好的安全性。TIME中CD8+、CD103+和CSF1-R+细胞密度增加的预后意义值得在类似临床环境中进一步评估。
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来源期刊
Clinical Cancer Research
Clinical Cancer Research 医学-肿瘤学
CiteScore
20.10
自引率
1.70%
发文量
1207
审稿时长
2.1 months
期刊介绍: Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.
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