Sequential Sorafenib and Sunitinib for Renal Cell Carcinoma

Purpose

Sorafenib and sunitinib are 2 tyrosine kinase inhibitors that were recently approved for renal cell carcinoma. In many patients sequential administration of the 2 drugs occurs because of the lack of sustained efficacy of the first agent. We determined the efficacy and safety of sequential administration.

Materials and Methods

To determine whether cross-resistance occurs between these 2 drugs we analyzed the outcome in 90 consecutive patients with renal cell carcinoma from 4 sites in France who had received the 2 drugs sequentially. All patients received sorafenib followed by sunitinib or vice versa. From 2003 to 2006, 68 patients received sorafenib, while 22 received sunitinib first.

Results

In the sorafenib-sunitinib group median progression-free survival was 26 weeks with sorafenib and 28 with sunitinib. In the sunitinib-sorafenib group median progression-free survival was 22 weeks with sunitinib and 17 with sorafenib. Median overall survival was 135 weeks in the sorafenib-sunitinib group and 82 weeks in the sunitinib-sorafenib group (HR 0.49, 95% CI 0.16 to 0.96, p = 0.04). The average duration of sequential administration was 61 and 49 weeks, respectively, in the sorafenib-sunitinib and sunitinib-sorafenib groups. Each sequence was well tolerated and no increase in grade 3-4 toxicity was observed.

Conclusions

Overall this retrospective study supports the conclusion of the lack of absolute cross-resistance between tyrosine kinase inhibitors. In this renal cell carcinoma population sorafenib followed by sunitinib was associated with longer survival than sunitinib followed by sorafenib. However, this observation needs further confirmation.

Key Words: kidney, carcinoma, renal cell, sorafenib, sunitinib, drug resistance

Abbreviations and Acronyms: IFN-α, interferon-α, IL-2, interleukin-2, MSKCC, Memorial Sloan-Kettering Cancer Center, mTOR, mammalian target of rapamycin, OS, overall survival, PD, progressive disease, PDGF, platelet-derived growth factor, PFS, progression-free survival, PR, partial response, R, receptor, RCC, renal cell carcinoma, SD, stable disease, SO, sorafenib, SU, sunitinib, TKI, tyrosine kinase inhibitor, VEGF, vascular endothelial growth factor, VHL, von Hippel-Lindau