Sunitinib in papillary renal cell carcinoma (pRCC): Results from a single-arm phase II study.

Abstract

4604 Background: Frontline sunitinib has been shown to produce a high response rate (RR), and improved progression-free survival (PFS) and overall survival (OS) in patients (pts) with clear cell RCC (ccRCC). Retrospective data suggest sunitinib may be effective in papillary and chromophobe RCC. We initiated a phase II trial of sunitinib in non-clear cell RCC (nccRCC), and report here on the pRCC subset. Methods: A two stage design was used to evaluate sunitinib (50 mg daily, 4 weeks on 2 weeks off) in nccRCC. Eligibility criteria included PS 0-2, measurable disease, and a maximum of 2 prior regimens. Pts with brain metastases were not excluded. Response assessment was performed at 6 wks, 12 wks and at 12 wk intervals thereafter. Primary endpoints were RR and PFS. Secondary endpoints were safety and OS. Results: Between 3/2007 and 5/2009, 23 pts with pRCC were enrolled (total nccRCC accrual 48). Median age was 64 (44-80). Fifteen pts (65%) had prior nephrectomy. Three pts (13%) had poor risk and 14 (61%) had intermediate risk disease by MSKCC criteria. Two pts had type I, 8 had type II, and 13 had pRCC type not specified. Three pts discontinued protocol treatment due to toxicity prior to completion of cycle 1 (one pt had MI 12 days after start of therapy), leaving 20 pts evaluable for response and PFS. All 23 pts were evaluable for toxicity and OS. There were no major responses. Eight pts had stable disease as best response. The radiologically assessed 6-mon PFS rate was 0.34 (95% CI, 0.18- 0.63). Median PFS was 1.6 months (95% CI, 1.3-12). Fifteen pts have died resulting in a median OS of 10.8 months (95% CI, 6.2-NE). Fewer disease sites, better performance status, prior nephrectomy, and normal baseline albumin and LDH levels correlated with longer OS. Common (> 1 pt) treatment related grade 3/4 toxicities included fatigue (6 pts), hypertension (3 pts), mucositis (3 pts), neutropenia (3 pts) and thrombocytopenia (2 pts). Dose reduction or interruption was required in 9 pts (39%). There were no treatment related deaths. Conclusions: In this phase II trial, sunitinib yielded no major responses and short PFS and OS underscoring the need to develop more effective therapies for pRCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer