Sunitinib: Ten Years of Successful Clinical Use and Study in Advanced Renal Cell Carcinoma

Abstract

The oral multikinase inhibitor sunitinib malate was approved by the U.S. Food and Drug Administration in January 2006 for use in patients with advanced renal cell carcinoma (RCC). Since then, it has been approved globally for this indication and for patients with imatinib-resistant or -intolerant gastrointestinal stromal tumors and advanced pancreatic neuroendocrine tumors. As we mark the 10-year anniversary of the beginning of the era of targeted therapy, and specifically the approval of sunitinib, it is worthwhile to highlight the progress that has been made in advanced RCC as it relates to the study of sunitinib. We present the key trials and data for sunitinib that established it as a reference standard of care for first-line advanced RCC therapy and, along with other targeted agents, significantly altered the treatment landscape in RCC. Moreover, we discuss the research with sunitinib that has sought to refine its role via patient selection and prognostic markers, improve dosing and adverse event management, and identify predictive efficacy biomarkers, plus the extent to which this research has contributed to the overall understanding and management of RCC. We also explore the key learnings regarding study design and data interpretation from the sunitinib studies and how these findings and the sunitinib development program, in general, can be a model for successful development of other agents. Finally, ongoing research into the continued and future role of sunitinib in RCC management is discussed.

The oncologist: 2017;22:41-52 IMPLICATIONS FOR PRACTICE: Approved globally, sunitinib is established as a standard of care for first-line advanced renal cell carcinoma (RCC) therapy and, along with other targeted agents, has significantly altered the treatment landscape in RCC. Research with sunitinib that has sought to refine its role via patient selection and prognostic markers, improve dosing and adverse event management, and identify predictive efficacy biomarkers has contributed to the overall understanding and management of RCC. Key learnings regarding study design and data interpretation from the sunitinib studies and the sunitinib development program, in general, can be a model for the successful development of other agents.

Keywords: Drug development; Renal cell carcinoma; Study design; Sunitinib; Treatment management.

Figure 1.

Range of median PFS and OS values in advanced RCC, before and after the era of targeted therapies. *, With TKIs as first‐ line mRCC therapy in primarily good‐ or intermediate‐risk patients [5], [6], [7], [8], [9], [10], [11], [12], [13]. Abbreviations: mRCC, metastatic renal cell carcinoma; OS, overall survival; PFS, progression‐free survival; RCC, renal cell carcinoma; TKIs, tyrosine kinase inhibitors.

Figure 2.

Kaplan‐Meier estimates of PFS from the pivotal phase III trial. From New England Journal of Medicine, Motzer RJ, Hutson TE, Tomczak P et al., Sunitinib Versus Interferon Alfa in Metastatic Renal‐Cell Carcinoma, 356,115–124, © 2007 Massachusetts Medical Society [12]. Reprinted with permission. Abbreviation: CI, confidence interval; PFS, progression‐free survival.