893P - Improved long-term clinical outcomes and safety profile of sunitinib dosing schedule with 4/2 switched to 2/1 in patients with metastatic renal cell carcinoma

Abstract

Background: Adverse events (AEs) have been a key issue for sunitinib administration with a standard dosing schedule. We aimed to identify the survival benefit and safety of alternative dosage schedules for sunitinib in patients with metastatic renal cell carcinoma (mRCC). Methods: Clinicopathologic and survival data of patients treated with sunitinib as first-line therapy were retrospectively reviewed. Patients were classified into three groups: a standard dosing schedule (4/2 schedule), alternative dosing schedule (2/1 schedule), and switched dosing schedule (4/2-2/1 schedule). Treatment-related AEs were recorded and evaluated. Progression-free survival (PFS), overall survival (OS), and potential risk factors were also analyzed. Results: A total of 99 patients were included. Seventy-five (75.8%) patients were initially administrated with a 4/2 schedule of sunitinib, while 24 were started with the 2/1 schedule. During treatment, 45 (60.0%) patients with an initial 4/2 schedule switched to a 2/1 schedule (4/2-2/1 schedule) due to severe AEs or poor tolerance. The median follow-up time was 37 months. Compared to that with a 4/2 schedule, patients with a 2/1 schedule had a much lower incidence of grade 3/4 AEs (69.6% vs. 40.6%, p = 0.001). Overall, the 4/2-2/1 schedule was associated with the best survival benefits. Among the 4/2, 2/1, and 4/2-2/1 schedule groups, the median PFS was 12.5, 11.0, and 25.0 months, respectively (p = 0.003), and the median OS was 21.0, 28.0, and 52.0 months, respectively (p = 0.030). Multivariate analysis identified the 4/2-2/1 schedule as an independent factor predicting favorable PFS. Although without statistical significance, 4/2-2/1 schedule could decrease 55% risk of death. Furthermore, patients with unfavorable IMDC risk seemed to have more opportunity to achieve better survival from the 4/2-2/1 dosing schedule. Conclusions: Among the three dosing schedules in the treatment of mRCC, patients with a 4/2-2/1 schedule could minimize treatment-related toxicities; more importantly, patients with 4/2-2/1 schedule could achieve a superior survival benefit. However, prospective clinical trials are required to identify the optimal sunitinib schedule. Legal entity responsible for the study: Sichuan University Funding: This work was supported by Natural Science Foundation of China (NSFC 81402110 from Pengfei Shen and NSFC 81672547 from Hao Zeng) and Science and Technology Support Program of Sichuan Province (2015SZ0230-3, Hao Zeng). Disclosure: All authors have declared no conflicts of interest.