cabozantinib and Head-and-Neck-Neoplasms

Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors, have immunomodulatory properties and have offered promising results when combined with anti-PD-1 agents. We conducted a phase 2, multicenter, single-arm trial of pembrolizumab and cabozantinib in patients with RMHNSCC who had Response Evaluation Criteria in Solid Tumors v.1.1 measurable disease and no contraindications to either agent. We assessed the primary end points of tolerability and overall response rate to the combination with secondary end points of progression-free survival and overall survival and performed correlative studies with PDL-1 and combined positive score, CD8

Topics: Head and Neck Neoplasms; Humans; Squamous Cell Carcinoma of Head and Neck; Vascular Endothelial Growth Factor A

Intestinal-type sinonasal adenocarcinoma is a rare epithelial malignancy primarily treated with surgery and chemoradiation. The combination of low-dose immunotherapy and a tyrosine kinase inhibitor in recurrent disease has not been previously studied.A man in his 20s with papillary adenocarcinoma of the sinonasal region, following surgical resection, was treated with six cycles of concurrent chemoradiotherapy, followed by four cycles of docetaxel, cisplatin and capecitabine. While on treatment, he was found to have extensive residual disease and he was started on low-dose nivolumab and cabozantinib. Repeat imaging after ten months of treatment revealed a significant reduction in lesions.Non-squamous head and neck cancers are often excluded from major trials, and the effect of immunotherapy in these histologies is poorly understood. The response seen with low-dose immunotherapy underscores the need for further research in this setting.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Head and Neck Neoplasms; Humans; Male; Nivolumab

Local or metastatic relapse following surgery, radiotherapy, and cisplatin is the leading cause of death in patients with head and neck squamous cell carcinoma (HNSCC). Our study shows overexpression of c-MET and AXL in HNSCC cells and patients resistant to radiotherapy and cisplatin. We demonstrate that cabozantinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), c-MET, and AXL, decreases migration, invasion, and proliferation and induces mitotic catastrophe and apoptotic cell death of naive and radiotherapy- and cisplatin-resistant HNSCC cells. Cabozantinib inhibits the growth and metastatic spread of experimental HNSCC in zebrafish and the growth of experimental HNSCC in mice by blocking tumor cell proliferation and angiogenesis. The efficacy of cabozantinib is also confirmed on viable sections of surgically removed specimens of human HNSCC and on a patient who relapses after five lines of treatment. These results suggest that cabozantinib is relevant for the treatment of patients with HNSCC after relapse under radiotherapy and cisplatin.

Topics: Anilides; Animals; Carcinoma; Cell Line, Tumor; Cisplatin; Head and Neck Neoplasms; Humans; Mice; Neoplasm Recurrence, Local; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-met; Pyridines; Receptor Protein-Tyrosine Kinases; Squamous Cell Carcinoma of Head and Neck; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays; Zebrafish