Sunitinib in patients (pts) with unresectable primary renal cell carcinoma (RCC)

Abstract

5096 Background: Sunitinib inhibits VEGF and related receptors, with high tumor shrinkage rates in metastatic (met) RCC. Shrinkage of primary tumors has been observed, although prospective investigation is lacking. The ability of sunitinib to convert primary RCC tumors from unresectable to resectable is of high clinical interest. Methods: Pts with histologically-confirmed RCC with an unresectable primary tumor with or without met disease were enrolled on a single-arm phase II trial. Primary tumors were unresectable due to ≥ 1 of the following: large tumor size, bulky lymphadenopathy, encasement of renal vessels, IVC thrombosis or proximity to vital structures. Pts received 50 mg sunitinib continuous dosing in repeated 6-week cycles. Staging by CT scans or MRI was done at baseline and every 2 cycles. A Simon 2-stage design was employed to test the alternative hypothesis of a conversion to resectability rate of 20% versus the null hypothesis of 5%; β = 0.8, α = 0.05 (n = 31). Results: 18 pts have been enrolled; 1 excluded due to a non-RCC diagnosis. Pts were unresectable due to bulky lymphadenopathy (6), IVC thrombosis (4), proximity to vital structures (4) or tumor size (3), although most pts had multiple factors. Median age among 14 evaluable pts was 61 years (range, 37–80), 59% male, 76% ECOG PS 0; 79% had distant met disease. The 14 evaluable pts have received a median of 3 cycles of therapy (range, 1–10+). Three pts (21%) have undergone primary tumor resection; viable RCC was identified in all specimens with no unexpected surgical morbidity. Nine pts (53%) had primary tumor reduction (median 19%; range, -64% to -1%). Overall, median best % change in tumor burden was 4.9% reduction for primary tumors (range, -43.1% to +8.5%) and 10.7% reduction for met sites (range, -89.5% to +28.6%). Median PFS is 4.9 months. Eleven pts (79%) discontinued therapy; 8 for PD, 1 for adverse events and 2 following surgery which removed all visible disease. Eight pts (57%) experienced grade 3 toxicity including thrombocytopenia, fatigue, hypertension, anemia, hemoptysis, and hand-foot syndrome; 1 pt had grade 4 neutropenia. Conclusions: Sunitinib has activity in unresectable primary RCC tumors, permitting resection in some pts. Continued prospective investigation is required to optimize patient selection and timing of surgery. [Table: see text]