The investigational oral drug MDV3100 significantly improved overall survival in patients with advanced prostate cancer, results of a large, phase III study show. The findings were presented today at the 2012 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium by lead investigator Howard Scher of Memorial Sloan-Kettering Cancer Center. Lab work conducted by Memorial Sloan-Kettering’s Charles Sawyers, a Howard Hughes Medical Institute investigator, and colleagues was instrumental in the development of this novel therapy.
The study presented today, called AFFIRM, randomized nearly 1,200 men – whose cancer continued to progress despite previous hormonal therapy and docetaxel chemotherapy – to receive either MDV3100 or placebo. Treatment with MDV3100 reduced the risk of death by 37 percent compared to placebo. As a result, the study was stopped in November of last year so patients in the placebo arm could be offered the drug.
“The results of the trial exceeded our expectations,” said Dr. Scher. “Prostate cancers that are progressing after standard hormones and chemotherapy are notoriously difficult to treat. It is extremely gratifying to see how the close integration of clinical observations and fundamental laboratory discoveries has come together to significantly improve patient outcomes and increase the growing arsenal of therapies for this population.
Most men with metastatic prostate cancer – cancer that has spread to bone or other parts of the body – often stop responding to first-line hormone therapies and develop a more aggressive form of the illness called castration-resistant prostate cancer (CRPC), the most advanced form of the disease. MDV3100 was co-invented by Dr. Sawyers and Michael Jung, PhD, Professor of Chemistry at the University of California, Los Angeles, after they uncovered that the reason men often build resistance to hormone therapy is due to an increase in the tumor’s production of androgen (male hormone) receptors. This insight led to the discovery of MDV3100, which is targeted specifically to bind to androgen receptors in cancer cells, inhibiting the ability of the receptor to drive cancer growth.
The results of the AFFIRM trial represent a significant milestone for me personally and professionally,” said Dr. Sawyers. “The basic research that led to the development of the drug, and the collaborative efforts to bring that discovery into a clinical setting should serve as a model for future drug development by academia. The pride in knowing that one’s work will impact patients’ lives is impossible to describe.
MDV3100 is also currently being investigated in men with CRPC who have not yet been treated with standard hormonal therapy or chemotherapy.