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

• DOI: 10.1158/1078-0432.c.7494004
• Publication Date: 2024-10-15T07:21:41Z
• Authors: 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
• Keywords: Cabozantinib

<div>AbstractPurpose:<p>Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent and/or metastatic head and neck squamous carcinoma (RMHNSCC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) have immunomodulatory properties improve clinical outcomes combination with anti-PD-1 different malignancies. We report the long-term efficacy safety pembrolizumab cabozantinib patients RMHNSCC include correlative biomarker analysis.</p>Patients Methods:<p>This open-label, single-arm, multicenter, phase 2 study screened 50 RMHNSCC, whom 36 received cabozantinib. The primary endpoint was overall response rate (ORR), safety, tolerability. Secondary endpoints included progression-free survival (PFS), (OS), studies tissue blood. PFS, OS, treated describe biomarkers evaluating p-MET expression tumor immune microenvironment (TIME) using multiplex immunohistochemistry.</p>Results:<p>With median follow-up 22.4 months, PFS 12.8 months 2-year 32.6% (95% CI, 18.8%–56.3%) OS 27.7 54.7% [95% confidence interval (CI), 38.9%–76.8%]. duration 12.6 38.5% 30.8%–81.8%). Long-term treatment-related adverse events manageable hypothyroidism (5.5%) grade elevated aspartate aminotransferase alanine (2.8%). Baseline correlated ORR (<i>P</i> = 0.0055). Higher density CD8<sup>+</sup>, CD103<sup>+</sup>, CSF1-R<sup>+</sup> cells at baseline improved [hazard ratio (HR) 5.27, <i>P</i> 0.030; HR 8.79, 0.017; 6.87, 0.040, respectively].</p>Conclusions:<p>Pembrolizumab provided prolonged encouraging disease control maintained favorable profile. prognostic significance higher TIME deserve further evaluation similar settings.</p></div>