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Sub-category:
Early/Localized disease, Locally Advanced/Recurrent/Advanced disease, and Biology
Category:
Genitourinary Cancers
Meeting:
2009 Genitourinary Cancers Symposium
Abstract No:
151
Author(s):
H. I. Scher, T. M. Beer, C. S. Higano, C. Logothetis, A. Anand, M. Hirmand, D. Hung, S. Larson, M. Fleisher, C. Sawyers, Prostate Cancer Clinical Trials Consortium; Memorial Sloan-Kettering Cancer Center, New York, NY; Oregon Health and Science University, Portland, OR; University of Washington, Seattle, WA; M. D. Anderson Cancer Center, Houston, TX; Medivation, San Francisco, CA
Abstract:
Background: Overexpression of the androgen receptor (AR) is frequent in CRPC. MDV3100 is a novel small molecule AR antagonist that, unlike bicalutamide, blocks nuclear translocation of AR DNA binding, and has no known agonist activity when AR is overexpressed. A phase 1/2 trial was initiated to determine safety, pharmacokinetics (PK), and antitumor activity, including effects on prostate-specific antigen (PSA), soft tissue and bone disease, circulating tumor cells (CTC), and [18F]-fluorodihydrotestosterone (FDHT) and [18F]-2-fluorodeoxyglucose (FDG) PET. Methods: Patients (pts) received MDV3100 orally, beginning at 30 mg/day with escalations in cohorts of 3-6, and after the safety of a dose established, enrollment expanded at ¡Ý60 mg/day to include 12 chemo-naive (naive) and 12 post-chemo pts. Results: 120 pts have been enrolled to date of whom 73 pts treated at 60, 150, and 240 mg/day and followed for 24+ weeks are reported here. MDV3100 has been generally well tolerated with no serious adverse events deemed related to study drug. PK were dose-linear with a half-life of approximately 1 week. Of the 42 naive and 31 post-chemo pts, 23 (55%) and 13 (42%) had a ¡Ý50% decline in PSA from baseline at week 12, respectively. At 240 mg/day, 8/28 pts (29%) had ¡Ý90% PSA decline from baseline. At 24 weeks, radiographic PR was observed in 5/13 pts (38%) at 240 mg/day with baseline evaluable soft tissue disease. Stable disease on bone scan was observed at 24 weeks in 6/21 pts (29%) with osseous disease on 240 mg/day. CTC counts available for 63/73 pts showed 85% of pts with favorable (<5) counts pretreatment maintained favorable posttreatment counts and 58% of pts at 240 mg/day converted from unfavorable (¡Ý5) to favorable posttreatment. 12 pts had FDHT and FDG PET. On FDHT scan, a >50% decline in the SUV max was observed in 11 (92%) at 4 and 12 weeks, while 6 (50%) had a decreased SUV max avg at 4 and 12 weeks on FDG. 31/73 pts (42%) received treatment >24 weeks. Conclusions: MDV3100 has been generally tolerated with encouraging anti-tumor activity as assessed by PSA declines, CTC changes, imaging findings, and time on treatment. The data suggest a dose-response trend with consistency across endpoints. MDV3100 appears to be a promising candidate for the treatment of CRPC.
Faculty Disclosures
Abstract Disclosures
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
Other Abstracts in this Sub-Category:
Abstracts by H. I. Scher:
Presentations by H. I. Scher:
Educational Book Manuscripts by H. I. Scher:
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