Presurgical sunitinib malate and androgen ablation in patients with localized prostate cancer at high risk for recurrence

Abstract

16004 Background: Presurgical androgen deprivation therapy (ADT) does not improve long-term outcomes in patients (pts) with high- risk localized prostate cancer (PCa). Sunitinib malate (SU) is an oral inhibitor of the tyrosine kinases of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET. Since the VEGF and PDGF signaling pathways have been implicated in angiogenesis and PCa progression, and ADT results in endothelial cell apoptosis in the prostate by a VEGF-mediated mechanism, we hypothesized that combined treatment with SU might improve the efficacy of ADT in this pt population. Methods: Pts with no radiological evidence of metastases and either PCa ≥ clinical (c)T3 disease or Gleason score (GS) 8–10 or serum prostate-specific antigen (PSA) ≥ 20 ng/mL or cT2b-c and GS 7 and PSA ≥10 ng/mL (AJCC, 1992), receive i.m. leuprolide and oral SU for three 30-day cycles followed by surgery. SU is administered continuously at 37.5 mg daily (25 mg daily in the initial 6 pts). The primary endpoint of this phase II trial is rate of pathologic complete response (pCR). Secondary endpoints include safety and time to PSA progression. Unresectable pelvic nodal disease, confirmed post-operative PSA ≥ 0.2 ng/mL, or administration of post-operative radiation or ADT, define treatment failure. Results: Forty-four pts have been enrolled, completing accrual, with a median age of 58 years (range 47–72); 34 Caucasian, 5 African-American, 4 Hispanic, and 1 Indian. High-risk criteria included cT3 (24/44), GS 8–10 (30/44), PSA ≥ 20 ng/mL (16/44). Two men were ineligible or declined therapy. Thirty-three pts have completed 3 months on treatment; no toxicity-related discontinuations or grade 4 toxicities have been observed. Grade 3 toxicities included hypertension (8), hand- foot syndrome (2), mucositis (2), fatigue (2), neutropenia (6), and hepatic (1). Thirty pts have completed surgery to date with no unexpected surgical complications. One pt experienced a pCR, while 3/30 (10%) have met the definition for treatment failure. Conclusions: The preoperative combination of SU and ADT appears to be safe and well tolerated in pts with high-risk primary PCa. One complete remission has been observed thus far. Ongoing analysis will allow us to determine if this strategy is worthy of further development. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Pfizer Oncology