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Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer postdocetaxel: Results from the phase III AFFIRM study.
General Poster Session A: Prostate Cancer
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: MDV3100, a novel androgen receptor signaling inhibitor (ARSI), competitively inhibits binding of androgens to the androgen receptor (AR), inhibits AR nuclear translocation, and inhibits association of the AR with DNA (Tran et al, Science. 2009;324:787). MDV3100 was selected for development based on activity in prostate cancer model systems with overexpressed AR, and was active in a phase I-II trial enrolling pre- and post-chemotherapy treated patients with progressive castration resistant disease (CRPC) (Scher et al, Lancet. 2010;375:1437). The AFFIRM trial evaluated whether MDV3100 could prolong overall survival (OS) in men with CRPC who progressed following docetaxel-based chemotherapy. Methods: In this randomized, double-blind, placebo-controlled, multinational phase III study (NCT00974311), patients who had received ≤ 2 regimens of docetaxel-based chemotherapy were randomized 2:1 to MDV3100 160 mg/day or placebo. Treatment with corticosteroids was allowed but not required. Patients were stratified by baseline ECOG performance status and mean brief pain inventory score. The primary endpoint was OS. Other efficacy endpoints included radiographic progression-free survival (PFS), time to first skeletal-related event, time to prostate-specific antigen (PSA) progression, and circulating tumor cell count conversion rate. Results: 1,199 patients were randomized between Sep 2009 and Nov 2010. Based on a planned interim analysis at 520 death events, the Independent Data Monitoring Committee (IDMC) recommended the study be unblinded and placebo patients offered MDV3100 due to a significant OS benefit (p<0.0001; hazard ratio 0.631). The estimated median OS was 18.4 months for MDV3100 treated compared to 13.6 months for placebo treated men, a median OS difference of 4.8 months. Data to be available include PFS, time to PSA progression, and safety. Conclusions: MDV3100, a novel ARSI, significantly improves OS in men with postdocetaxel-treated CRPC reducing the risk of death by 37% relative to placebo. The IDMC determined the risk:benefit of MDV3100 was favorable and recommended the phase III AFFIRM trial be unblinded.
Abstracts by Howard I. Scher:
A phase 2 study of BIND-014 (PSMA-targeted docetaxel nanoparticle) administered to patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).Meeting: 2016 Genitourinary Cancers Symposium | Abstract No: 233
A phase I/IIa trial of prostate specific membrane antigen (PSMA) positron emission tomography (PET) imaging with 89Zr-Df-IAB2M in metastatic prostate cancer (PCa).Meeting: 2016 Genitourinary Cancers Symposium | Abstract No: 287
- Meeting: 2016 Genitourinary Cancers Symposium | Abstract No: 302
Presentations by Howard I. Scher:
Impact of on-study corticosteroid use on efficacy and safety in the phase III AFFIRM study of enzalutamide (ENZA), an androgen receptor inhibitor.Meeting: 2013 Genitourinary Cancers Symposium Abstract No: 6Session: Oral Abstract Session A: Prostate Cancer (eQ&A) (Oral Abstract Session)