Sunitinib malate for metastatic castration resistant prostate cancer following docetaxel-based chemotherapy

Abstract

5157 Background: Sunitinib malate is a multitargeted tyrosine kinase inhibitor approved multinationally for renal cell carcinoma and gastrointestinal stromal tumors. Effective options are lacking for progressive CRPC (castration-resistant prostate cancer) following conventional chemotherapy. This phase II trial was conducted to examine the efficacy and toxicity of sunitinib in metastatic CRPC progressing after prior chemotherapy. Methods: Key inclusion: histologically confirmed adenocarcinoma (metastatic stage IV), clinical or PSA progression, currently on androgen ablation treatment, with 1- 2 prior chemotherapy regimens including docetaxel. Other standard (drug specific) inclusion/exclusion criteria applied. The primary objective was clinical progression-free survival (PFS) with a 12-week PFS >30% as a goal. Secondary objectives: PSA response, objective response, quality of life, pain, survival, and toxicities. Sunitinib 50 mg/day was administered orally 4 weeks on / 2 weeks off in 6-week cycles. Patients (pts) were treated to a maximum of 8 cycles or until clinically progressive disease or intolerable toxicity. A planned interim analysis of the first 19 pts is presented here; accrual goals (n=36) have been met. Results: The median age was 69 years. The median clinical PFS (as per RECIST, bone events, pain, obstruction, ECOG) for these pts was 2.8 months (95% CI, 2.2, 6.1) with a 12-week PFS attained in 48.3%. A 50% PSA response was seen in 1 pt, and 30% PSA response was seen in 3 pts, with an additional 2 pts with unconfirmed 30% PSA responses. Grade 3–4 therapy related toxicities were infrequent with only Grade 3 anemia occurring in 2 pts; 7 pts died due to disease progression with 2 deaths deemed possibly related to sunitinib (non- neutropenic sepsis and hemorrhagic stroke, n=1 each). Conclusions: Single-agent sunitinib malate demonstrated significant antitumor activity with manageable toxicities in men with metastatic CRPC that had progressed following 1–2 prior regimens including docetaxel. Accrual is complete and final efficacy and toxicity data on all pts will be presented. These data warrant further evaluation of sunitinib in metastatic CRPC. Supported, in part, by a grant from Pfizer, Inc., New York, NY. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, GlaxoSmithKline, Pfizer Oncology, Wyeth Bayer, GlaxoSmithKline, Pfizer Oncology, Wyeth Bayer, GlaxoSmithKline, Pfizer Oncology, Wyeth