Sunitinib dosing, toxicity, and outcomes in first-line advanced renal cell carcinoma (aRCC): A U.S. Oncology Network (USON) retrospective study.

Abstract

e15089 Background: Sunitinib is a first-line therapy for patients (pts) with aRCC. As a multitargeted tyrosine kinase inhibitor (TKI), it is associated with toxicities that may impact dosing; dose reductions may result in inferior clinical outcomes (Motzer, 2011 ASCO GU, abstract LBA308). This retrospective study was initiated by USON to evaluate dosing patterns of first-line sunitinib, and its association with toxicities and outcomes in community practices. Methods: Pts with aRCC who started first-line sunitinib between June 1, 2007 and May 31, 2011 at 17 USON practices were identified; clinical data were extracted by chart review from iKnowMed electronic medical records that were linked to USON retail pharmacy database. Pts who were enrolled in clinical trials or receiving care for other primary tumors were excluded. Results: Pt characteristics: N=134; median age = 64 years (range 41–87); ECOG PS 0/1 = 85%; clear cell RCC = 81%; and nephrectomy = 61%. Objective response rate was 16%. Overall survival (OS) was 15.4 months (95% confidence interval 11.9–20.8). Median treatment duration was 4 cycles (range 1–19): 27 pts (20.1%) received only 1 cycle of sunitinib (23 at full dose [50 mg] and 4 at <full dose); 107 pts (79.9%) received >1 cycle of sunitinib (53 received full dose; 35 started at full dose but were dose-reduced; 14 always received <full dose; 5 started at <full dose but were dose-increased to 50 mg). Overall, 45 pts were dose-reduced, principally (93%) due to toxicities; 67% of all dose reductions occurred in the first 3 cycles. 121 pts discontinued sunitinib after completing at least 1 cycle, mostly due to disease progression (PD; 44%) or toxicities (17%); 74% of all discontinuations occurred within the first 5 cycles. Conclusions: RCC pts in community practices commonly undergo sunitinib dose reductions in the first 3 cycles due to toxicities, and discontinue therapy within the first 5 cycles due to PD. The median number of cycles and OS were lower than those reported in clinical trials (Motzer JCO 2009;27:3584–3590). More selective TKIs are needed to reduce toxicities, optimize dosing, and potentially improve outcomes. Funded by a grant from AVEO Pharmaceuticals, Inc.