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. We report the long-term efficacy and safety of pembrolizumab and cabozantinib 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. 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, safety, and describe correlative biomarkers.
Results: With median follow-up of 22.4 months, median PFS was 12.8 months 2-year PFS of 32.6% (95%CI 18.8-56.3%) and median OS of 27.7 months,2-year OS of 54.7% (95%CI 38.9-76.8%). Median duration of response was 12.6 months, with 2-year rate of 38.5% (95%CI 30.8-81.8%). Long-term TRAEs included manageable hypothyroidism (5.5%) and grade 1 elevated AST and ALT (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).
Conclusion: Pembrolizumab and cabozantinib provided prolonged encouraging long-term disease control and survival with a maintained favorable safety profile. The prognostic significance of increased CD8+, CD103+ and CSF1-R+ cell density in TIME deserve further evaluation in similar clinical settings.