J Cancer 2018; 9(18):3303-3310. doi:10.7150/jca.25693
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
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China, 610041
*These three authors are co-first authors of the manuscript
Zhang X, Sun G, Zhao J, Shu K, Zhao P, Liu J, Yang Y, Tang Q, Chen J, Shen P, Wang J, Zeng H. 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. J Cancer 2018; 9(18):3303-3310. doi:10.7150/jca.25693. Available from http://www.jcancer.org/v09p3303.htm
Purpose: This study aimed to identify the survival benefit and safety of alternative dosage schedules for sunitinib in metastatic renal cell carcinoma.
Materials and 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).
Results: Ninety-nine patients were retrospectively 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 adverse events (AEs) or poor tolerance. 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=0.03). 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.
Conclusion: 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.
Keywords: clinical outcome, dosing schedule, metastatic renal cell carcinoma, sunitinib, safety profile