Pazopanib Plus Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
As reported in The Lancet Oncology by Adkins et al, the addition of the angiogenesis inhibitor pazopanib (Votrient) to cetuximab (Erbitux) in a phase Ib and expansion cohort study showed activity in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
In the single-center trial, 22 patients were enrolled between June 2013 and April 2017 into a dose-escalation phase and received pazopanib oral suspension daily in 8-week cycles at 200, 400, 600, or 800 mg/d along with cetuximab given intravenously once per week at 400 mg/m² for the first dose and 250 mg/m² in subsequent cycles. Among these patients, 20 had distant or distant and local/regional recurrence and 17 had received ≥ 1 line of therapy for recurrent or metastatic disease. An additional 9 patients were enrolled at the selected phase II dose; of these, 7 had distant or distant and local/regional recurrence and 5 had received ≥ 1 line of prior therapy.
Phase II Dose Selection and Responses
No maximum tolerated dose of pazopanib plus cetuximab was reached in the dose-escalation phase. Single dose-limiting grade 3 adverse events were observed with pazopanib at 400 mg/d (neutropenia with infection), 600 mg/d (proteinuria), and 800 mg/d (fatigue). The phase II dose selected for the combination was pazopanib at 800 mg/d during 8-week cycles plus cetuximab at 400 mg/m² on day 1 of cycle 1 and then 250 mg/m² weekly.
Among all 31 patients, the most common grade 3 or 4 adverse events were hypertension (32%), decreased lymphocytes (23%), and dysphagia (23%). Grade 3 adverse events attributed to pazopanib included hypertension, anemia, fatigue, hypoalbuminemia, and venous thromboembolism (no grade 4 events observed). No treatment-related deaths occurred.
Objective response was observed in 11 patients (35%), including complete response in 2 (6%). Response was observed in 6 (55%) of 11 patients with platinum-naive and cetuximab-naive disease, 3 (25%) of 12 with cetuximab-resistant disease, and 5 (28%) of 18 with platinum-resistant disease.
The investigators concluded, “Pazopanib oral suspension at a dose of 800 mg/d was feasible to administer in combination with standard weekly cetuximab for patients with recurrent or metastatic HNSCC. Encouraging preliminary antitumour activity was observed with this combination therapy and warrants further validation in randomised trials.”
The study was supported by GlaxoSmithKline and Novartis.
Douglas Adkins, MD, of Washington University School of Medicine, Division of Medical Oncology, is the corresponding author for the Journal of Clinical Oncology article.
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