Schedule modifications and treatment outcomes for sunitinib-related adverse events.

Abstract

e15115 Background: Sunitinib is a front-line therapy for metastatic renal cell cancer (mRCC). Recommended dose is 50 mg daily; 4 wk on, 2 wk off (4/2) schedule. Sunitinib is associated with several adverse events (AEs). An ideal dose modification algorithm is not known. We sought to identify 1) commonly occurring AEs, 2) schedule modifications (SM) that maintained dose intensity while decreasing AEs, and 3) the impact of SM on 6 mo follow-up (f/u). Methods: Retrospective review of mRCC pts in an outpatient clinic was performed from 1/1/08 to 5/31/09. Pts ≥ 18 years of age with clear cell mRCC on sunitinib therapy with ≥ 6 mo f/u were eligible. At first intolerable AE, pts were switched from a 4/2 schedule to a 2/1 schedule, or further adjusted to a 7 day on/3 day off or other schedule. Pt characteristics including demographics, disease status, laboratory data, AEs, SMs and treatment outcomes were analyzed. Results: 74 eligible pts were identified; preliminary data from 31 pts are presented. Median age was 66 yrs; 23% had prior systemic therapy; 32% were good, 48% intermediate and 20% poor prognosis by MSKCC criteria. Pts had median 2 visceral mets and 49% had primary tumor in place. At baseline, all pts received sunitinib 50 mg daily on schedules shown in the Table. AEs included fatigue (51%), diarrhea (35%), hand-foot syndrome (32%), and mucositis (29%). Dose intensity was maintained in 81% of pts at 6 mo f/u. SM were common (Table). For the 25 pts initiated on a 4/2 schedule, 7 discontinued for PD and 3 for toxicity at 6 mo. All 6 pts initiated on a 2/1 schedule continued on sunitinib at 6 mo at the original dose intensity and schedule, whereas 13 of 15 remaining pts initiated on a 4/2 schedule had switched to an alternate schedule (p=0.0005, 95% CI 0.0752-0.830). Median treatment duration (MTD) was 10 mo for all pts. At last available f/u, 29% of pts continue on sunitinib therapy with MTD of 15.3 mo, and 89% of pts are on an alternate dosing schedule. Conclusions: In this group of pts, sunitinib SM maintained high dose intensity and did not appear to adversely impact outcome. Prospective investigations of alternate sunitinib dosing schemas may be warranted. (%) Sunitinib Schedule 4/2 2/1 7/3 alt 7/4 Other Baseline 100 77 19 3 1 6-mo follow-up 68 10 48 29 13 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Pfizer Bayer, Genentech, Pfizer