SU011248, a novel tyrosine kinase inhibitor, shows antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma: Results of a phase 2 trial

Abstract

4500 Background: SU011248 is an oral multi-targeted tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity through inhibition of PDGFR, VEGFR, KIT and FLT3. Methods: 63 patients with metastatic renal cell carcinoma (RCC) were treated with repeat cycles of SU011248 orally at 50 mg daily for 4 weeks followed by a 2-week rest period. Eligibility included measurable disease, ECOG performance status of 0 or 1, failure of one prior cytokine-based therapy, and adequate cardiac function. Results: The median age of patients was 60 years and 58 patients (92%) had prior nephrectomy. Best response to SU011248 as assessed by RECIST: Of 15 (24%) patients who achieved a PR, 1 patient progressed at 5 months and 14 remain progression-free with median duration of response of 6+ months. Of 29 patients with best response of SD, 5 (8%) patients had reduction of unidimensional measurement of at least 30% and await confirmation of response status. Currently there are 32 patients on treatment with continued PR/SD with median follow-up of 6+ months. Safety data on 63 patients indicates an acceptable toxicity profile with mostly grade 1/2 events including fatigue/asthenia (78%), nausea (56%), diarrhea (51%), and stomatitis (44%). Grade 3/4 toxicities include lymphopenia (30%), elevated lipase (21%) and amylase (8%) without clinical signs of pancreatitis, and fatigue/asthenia (8%). Two patients were taken off the study for decreases in left ventricular ejection fraction > 20% without clinical symptoms. Conclusions: SU011248 administered in repeat cycles of 50 mg daily for 4 weeks followed by a 2-week rest period exhibits promising antitumor activity as second-line therapy for patients with metastatic RCC. Additional studies are planned to further assess the role of SU011248 in the treatment of metastatic RCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Inc. Pfizer, Inc. Pfizer, Inc. Pfizer, Inc. Pfizer, Inc.