(ChemotherapyAdvisor) – MDV3100, a novel androgen receptor signaling inhibitor (ARSI), significantly improved overall survival (OS) in men with castration-resistant prostate cancer previously treated with docetaxel. Results of the phase 3 randomized, double-blind, placebo-controlled AFFIRM trial were reported at the 2012 Genitourinary Cancers Symposium.

“This drug targets a unique aspect of the malignant process, blocking a biological mechanism that enables tumors to resist other therapies and grow – and it worked far better than we expected when we set out,” said lead author Howard I. Scher, MD, of Memorial Sloan-Kettering Cancer Center, New York, of the results. MDV3100 is the first in a new class of ARSIs that affects multiple steps in the androgen receptor signaling pathway.

Between September 2009 and November 2010, 1,199 patients who had received ≤2 regimens of docetaxel-based chemotherapy were randomized 2:1 to oral MDV3100 160mg/day or placebo.

After a planned interim analysis at 520 death events, the investigators found that median OS, the primary end point, was 18.4 months for the MDV3100 arm vs 13.6 months for the placebo arm, a median OS difference of 4.8 months (P<0.0001; HR=0.631). The study was unblinded and patients in the placebo arm offered MDV3100.

Median radiographic progression-free survival was 8.3 months for the MDV3100 arm vs. 2.9 months for placebo. Almost 30% of patients had complete or partial responses to MDV3100 treatment on imaging vs. 1.3% for placebo. MDV3100 significantly reduced PSA 50% or greater from baseline in 54% of patients vs. 1.5% in the placebo arm; reduction of 90% or greater from baseline was observed in 25% and 1%, respectively. Overall, MDV3100 increased time to PSA progression by 5.3 months (-3.0 months in the placebo arm to 8.3 months in the MDV3100 arm).

“MDV3100 was well-tolerated, and the benefit:risk profile will likely position it as the front-line agent post-docetaxel therapy,” Dr. Scher said. The most common adverse events occurring more frequently in the MDV3100 arm vs. placebo were fatigue, diarrhea, and hot flushes.

Maximizing use of MDV3100 is being explored, including in sequence or combination with other agents. Trials of MDV3100 in earlier stages of prostate cancer are ongoing.

The 2012 Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

Abstract

Clinical Trial