A single-center retrospective review of outcomes associated with sunitinib alternative schedule compared to traditional schedule.

Abstract

381 Background: Sunitinib is a front-line therapy for metastatic renal cell cancer (mRCC). Recommended dose is 50 mg daily; 28 days (d) on/14 d off (traditional schedule; TS). Sunitinib is associated with several adverse events (AEs). An ideal treatment modification algorithm is not known. We sought to identify (1) common AEs, (2) alternative schedules (AS) that maintained dose intensity while decreasing AEs, and (3) the impact of AS on outcomes. Methods: Single-center retrospective review of mRCC pts performed from January 26, 2006 to March 1, 2011. Pts > 18 years of age with mRCC who received first-line antiangiogenic therapy with sunitinib were eligible. A subset of pts were switched at first intolerable AE from TS to a 14 d/7 d, or further adjusted to 7 d /3 d, or other AS. Control group underwent standard dose reduction. Pt characteristics including demographics, disease status, laboratory data, AEs, AS, and treatment outcomes were analyzed. Results: 186 eligible pts were identified. At baseline, 87% received sunitinib 50 mg and 88% were on TS. 99 pts (53%) continued TS and 87 pts (47%) were switched to AS. Baseline characteristics were similar. Median age was 61 yrs; by MSKCC criteria 5% were good, 50% intermediate, and 45% poor prognosis. Pts had median 2 visceral mets and 42% had primary tumor in place. AEs included fatigue (47%), diarrhea (24%), and hand-foot syndrome (26%). Median time to AS was 126 d with 14 d/7 d the most common (82%). Median time on treatment was 14.9 months (mo) (95% CI:10.2 – 17.0 mo) in AS pts vs. 4.2 mo (95% CI: 3.6 – 5.7 mo), respectively (p < 0.0001). Median OS was 32.9 mo (95% CI:28.3-54.1 mo) vs. 18.5 mo (95% CI: 10.3-21.5 mo), respectively (p = 0.0001). ECOG PS > 2 (HR 3.9), elevated LDH (HR 2.04), and > 2 mets (HR 1.79) were associated with decreased OS. MSKCC intermediate vs. poor (HR 0.57) and AS (HR 0.54) were associated with improved OS by multivariate regression analysis (p < 0.05). Conclusions: In our cohort study, AS sunitinib significantly prolonged outcomes and was predictive of OS. Prospective investigations of alternate dosing schemas are warranted.