In a phase I study from Memorial Sloan Kettering Cancer Center (MSK), New York, the combination of cabozantinib and cetuximab showed antitumor efficacy in heavily pretreated patients with recurrent or metastatic head and neck squamous cell cancer.1
“The combination of cabozantinib and cetuximab showed antitumor efficacy in heavily pretreated patients with recurrent or metastatic head and neck squamous cell cancer.”— Antoine Desilets, MD
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Antoine Desilets, MD, an advanced oncology fellow at MSK who presented the findings in a poster at the 2023 ASCO Annual Meeting,1 explained the rationale for this combination. “EGFR targeting with cetuximab is a standard therapy for head and neck squamous cell carcinoma. Resistance to chemotherapy can be mediated by activation of the receptor tyrosine kinase AXL. Cabozantinib is a tyrosine kinase inhibitor of AXL/c-MET/VEGF, with antitumor activity in preclinical models of this tumor, so we conducted a phase I trial to assess the combination of cabozantinib and cetuximab.”
The study evaluated 20 patients, 65% of whom had oropharyngeal cancer (including 85% who tested positive for human papillomavirus [HPV]). Patients were heavily pretreated, including prior immunotherapy (95%), chemotherapy (95%), cetuximab (80%), and tyrosine kinase inhibitors (10%). Patients received an initial cetuximab loading dose of 400 mg/m2 followed by 250 mg/m2 weekly; the maintenance dose was later amended to 500 mg/m2 biweekly. Cabozantinib was given concurrently on days 1 to 28 of each 28-day cycle, with starting doses of 40 mg for the first 11 patients and 60 mg for the remaining 9 patients.
Outcomes in Refractory Population
In the overall population, median progression-free survival was 3.4 months, and median overall survival was 8.1 months. Survival outcomes were best for patients with HPV-associated oropharyngeal cancer, whose median progression-free survival was 7.1 months, vs 3.1 months for HPV-negative tumors (P = .047). “After adjustment for age, performance status, and dose of cabozantinib, patients with HPV-associated tumors had an 83% reduction in the risk of disease progression,” Dr. Desilets reported.
The most common clinically relevant grade 3 or 4 adverse events were increased liver enzymes and bilirubin as well as hand-foot syndrome. Dose reductions of cabozantinib were necessary for 36% of patients who started on 40 mg and 55% of those started on 60 mg.
DISCLOSURE: Dr. Desilets reported no conflicts of interest.
1. Desilets A, Pfister DG, Wong W, et al: A phase 1 study of concurrent cabozantinib and cetuximab in recurrent or metastatic head and neck squamous cell cancer. 2023 ASCO Annual Meeting. Abstract 6025. Presented June 5, 2023.