Pazopanib plus cetuximab may be a feasible and well-tolerated treatment option among patients with resistant or metastatic head and neck squamous cell carcinoma (HNSCC), according to a study published in The Lancet Oncology.1

Previous studies have shown that EGFR activation and an increase in angiogenesis are hallmark characteristics of HNSCC. Despite evidence suggesting benefit, only a few studies have investigated the effectiveness of pazopanib plus cetuximab, an angiogenesis inhibitor and EGFR inhibitor respectively, for HSNCC.

For this phase 1b study (ClinicalTrials.gov Identifier: NCT01716416), researchers enrolled 22 patients with confirmed recurrent or metastatic HNSCC into a dose-escalation trial using a 3+3 design; 9 additional patients were enrolled into the expansion cohort. In the dose-escalation stage, patients were given pazopanib 200 mg, 400 mg, 600 mg, or 800 mg oral suspension daily plus fixed-dose cetuximab weekly.

Results showed that a maximal tolerated dose of pazopanib was not reached. Only 1 grade 3 adverse event (AE) occurred during the dose-escalation phase for each pazopanib level; neutropenia with infection with the 400 mg dose, proteinuria with the 600 mg dose, and fatigue with the 800 mg dose. Investigators determined that the recommended phase 2 dose for this regimen was pazopanib 800 mg daily plus cetuximab 400 mg/m2 cycle 1 followed by 250 mg/m2 weekly.

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Of the 9 patients enrolled in the expansion cohort, the most frequently reported grade 3 to 4 AEs included hypertension (32%), lymphocyte count decrease (23%), and dysphagia (23%). No treatment-related deaths were observed.

The overall response rate was 35% (11 of 31 patients), including 6% (2) complete response and 29% (9) partial response. Tumor responses were observed in 55% (11) of patients who were platinum- and cetuximab-naïve, 25% (3) who were cetuximab-resistant, and 28% (5) of patients with platinum-resistant disease.

The authors concluded that “encouraging preliminary anti-tumor activity was observed with this combination therapy, even in patients with cetuximab-resistant or platinum-resistant HNSCC; these results warrant further validation in randomized trials.”

Reference

  1. Adkins D, Mehan P, Ley J, et al. Pazopanib plus cetuximab in recurrent or metastatic head and neck squamous cell carcinoma: an open-label, phase 1b and expansion study [published online July 9, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30350-4