A Phase 2 Trial of Sunitinib in Patients with Advanced Non-clear Cell Renal Cell Carcinoma

Background: Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC). Objective: To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC. Design, setting, and participants: This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with >= 20% sarcomatoid histology, performance status 0-2, measurable disease, a maximum of two prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors. Intervention: Patients received sunitinib 50 mg daily on a 4-wk on, 2-wk off schedule. Outcome measurements and statistical analysis: Primary end points were objective response rate (ORR) and progression-free survival (PFS). Secondary end points were safety and overall survival (OS). Results and limitations: Fifty-seven patients were eligible (nccRCC histology: papillary, 27; chromophobe, 5; unclassified, 8; collecting duct or medullary carcinoma, 6; sarcomatoid, 7; and others, 4). Median PFS for 55 evaluable patients was 2.7 mo (95% confidence interval [CI], 1.4-5.4). Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 mo (95% CI, 1.4-5.4). Median PFS for patients with chromophobe histology was 12.7 mo (95% CI, 8.5-NA). Median OS for all patients was 16.8 mo (95% CI, 10.7-26.3). Treatment-emergent adverse events were consistent with sunitinib's mechanism of action. The nonrandomized design and small number of patients are limitations of this study. Conclusions: The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.