Pazopanib Plus Cetuximab May Be Effective and Well-Tolerated in Head and Neck Cancer
Only a few studies have investigated the effectiveness of pazopanib and cetuximab, an angiogenesis inhibitor and EGFR inhibitor, respectively, for head and neck squamous cell carcinoma.
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.
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.”
- 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