UKMCC-01: A phase II study of pazopanib (PAZ) in metastatic Merkel cell carcinoma.

9542Background: The clinical activity of pazopanib, a multi-targeted tyrosine kinase inhibitor, was evaluated in metastatic Merkel Cell Carcinoma (MCC) following a case report demonstrating benefit in a phase II clinical trial. Methods: Patients with histologically confirmed unresectable metastatic MCC received pazopanib at a starting dose of 800mg or 600mg daily, as clinically indicated, following written informed consent. Chemotherapy pre-treated or naïve patients were eligible. This was a single arm, multi-center, UK, phase II trial using a Simon two-stage minimax design (p0 = 0.05, p1 = 0.20, alpha = 0.15, power = 90%). The primary outcome was clinical response rate measured by RECIST. In order to progress to the second stage, 1 responder was required in the first 19 patients, with; 3 or more responders in 25 patients required to confirm adequate activity for further clinical investigation. Results: Seventeen patients with histologically proven MCC were recruited between Jan-13 and Jan-16, when the trial was stopped as the primary objective of at least 3 responses was met and accrual was slow in this rare disease. The median age was 73 years (range 56 to 90). The median duration of treatment with pazopanib was 8.0 weeks (range 1.3 to 38.4). Patients discontinued treatment due to toxicity (2) and progression (13); 2 patients are still on treatment. At the time of reporting, 16/17 patients were evaluable: 3/16 partial responses were observed (response rate; 19%, lower 85% Wilsons confidence interval; 9%); a further 6 patients had SD with clinical benefit therefore seen in 9/16 (56%). Median progression-free survival time was 3.2 months (95% CI 1.4, 5.2) and median overall survival time was 6.4 months (95% CI 3.9, 13.2). Adverse events were comparable to those previously observed in trials in soft tissue sarcoma and renal cell carcinoma with pazopanib. Conclusions: Pazopanib has clinical activity in advanced MCC and warrants further investigation in this rare and poor prognosis cancer. Funded by Cancer Research UK (CRUK/11/015) with free drug and an educational grant from GlaxoSmithKline/Novartis. Clinical trial information: 10125877.