Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 4522
© 2006 American Society of Clinical Oncology

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Abstract

Efficacy and safety of sunitinib malate (SU11248) in bevacizumab-refractory metastatic renal cell carcinoma (mRCC)

Cleveland Clinic Foundation, Cleveland, OH; Duke University, Durham, NC; Massachusetts General Hospital, Boston, MA; University of California San Francisco, San Francisco, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; City of Hope, Los Angeles, CA; Baylor Charles A. Sammons Cancer Center, Dallas, TX; Pfizer Inc., La Jolla, CA

4522

Background: Sunitinib malate (SU11248) is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptor (VEGFR) family, platelet-derived growth factor receptor (PDGFR) and other related receptors. It has demonstrated anti-tumor activity in cytokine-refractory mRCC patients (pts). The activity of sunitinib in pts refractory to VEGF binding agents such as bevacizumab, however, has not been evaluated. It was hypothesized that tumor resistance to bevacizumab may be driven, in part, through pathways sensitive to inhibition by sunitinib. A phase II study evaluating the activity of sunitinib in bevacizumab-refractory mRCC was thus conducted. Methods: Pts with mRCC who demonstrated RECIST-defined disease progression within 3 months after bevacizumab-based therapy were treated with sunitinib (50 mg daily, 4 weeks of a 6-week cycle). Additional eligibility included measurable disease, clear cell histology, 2 prior systemic regimens, prior nephrectomy, performance status 0 or 1 and adequate organ function. The primary endpoint was objective response by RECIST criteria. A single-stage design was employed to test the null hypothesis that the true response rate is 5% versus the alternative hypothesis that the true response rate is 15%. Results: Accrual of 60 patients has been completed. Baseline characteristics include a median age of 59 years; 92% of pts had 2 metastatic sites and 23% had prior radiotherapy. Thirty-two of 60 pts enrolled are evaluable for response; 28 pts are too early for assessment. Twenty-six pts (81%) demonstrated some degree of tumor shrinkage, including, 4 pts (13%; 95% CI 4%, 29%) demonstrating an objective partial response. The most common treatment-related adverse events (AEs) included fatigue, diarrhea, dysgeusia, and nausea. Serious treatment-related AEs included fatigue, diarrhea, nausea and one fatal cerebral hemorrhage; 3 pts withdrew due to an AE. Conclusions: Sunitinib has substantial antitumor activity in bevacizumab-refractory mRCC pts, suggesting that sunitinib may inhibit signaling pathways involved in bevacizumab resistance. The precise mechanisms of response to sunitinib in bevacizumab-refractory tumors will require additional studies.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Abbott, Antigenics, GlaxoSmithKline, Pfizer Pfizer Bayer, Genentech, GlaxoSmithKline, Pfizer, Wyeth Bayer, Celgene, Genentech, GlaxoSmithKline, Pfizer, Protein Design Labs, Wyeth

Abstract presentation from the 2006 ASCO Annual Meeting