In the Pipeline

SAN FRANCISCO – MDV3100, new oral inhibitor of androgen receptor signaling, reduces the risk of death by more than a third after a failure of docetaxel chemotherapy in men with progressive castration-resistant prostate cancer, according to results of the randomized AFFIRM trial.

Interim data for the trial, which was conducted in nearly 1,200 men, showed that those given the investigational drug lived 4.8 months longer than their counterparts who had been given a placebo, corresponding to a 37% reduced risk of death, lead investigator Dr. Howard I. Scher reported at the Genitourinary Cancers Symposium. This positive finding triggered early trial closure.

Dr. Howard I. Scher

Additional analyses revealed that men treated with the drug were significantly more likely to have a soft tissue response and to have at least a halving of their prostate-specific antigen (PSA) level. At the same time, there was no increase in the rate of higher-grade adverse events; seizures (a potential concern from earlier research) occurred at low frequency.

"MDV3100 now joins the list of drugs demonstrating a survival benefit in a phase III trial post docetaxel," adding to abiraterone (Zytiga) and cabazitaxel (Jevtana), Dr. Scher maintained. "The risk-benefit ratio will likely position this as the frontline agent post docetaxel therapy."

"I’m not the [Food and Drug Administration], but I would say that when you see this kind of survival benefit and safety profile – and looking at a prior drug [investigation] that I had a privilege of leading – I would say that this should be approved relatively quickly," he commented in a press briefing.

"I have only one comment: wow! That’s very impressive," said Dr. Nicholas J. Vogelzang, the moderator of the briefing and the chair and medical director of the Developmental Therapeutics Committee of US Oncology. The median survival and dramatic rates of PSA reduction seen with MDV3100 are "unprecedented. This is going to definitely change the way we take care of patients every day in the office."

"This is a landmark study," Dr. Adam S. Kibel agreed in an interview at the meeting. "I think this is a drug that will be widely used, assuming it gets FDA approved."

Dr. Adam Kibel

Initially, MDV3100 is likely to be used in the postdocetaxel space, said, Dr. Kibel, chief of urology at Brigham and Women’s Hospital and the Dana Farber Cancer Institute and a professor at Harvard Medical School, all in Boston. "I imagine that it would probably be the first-line drug because it appears to have a little less side effect profile than abiraterone and certainly lower than cabazitaxel."

"The one tripper in there is, will insurance pay for it and how much is it going to cost?" said Dr. Kibel.

MDV3100 is also being tested in patients who have not yet received docetaxel. "I will be shocked if [those data] are not positive," he commented. And should it perform well there, "it will move prior to docetaxel, because it appears to be very well tolerated from the data presented."

02/03/12  

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FROM THE GENITOURINARY CANCERS SYMPOSIUM

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Vitals

Major Finding: Overall survival was significantly longer in the MDV3100 group than in the placebo group (18.4 vs. 13.6 months; HR, 0.63), and there was no increase in the rate of grade 3 or higher adverse events.

Data Source: The AFFIRM trial is a randomized phase III trial comparing MDV3100 vs. placebo in 1,199 patients with progressive castration-resistant prostate cancer who had experienced failure of docetaxel.

Disclosures: Medivation sponsored the trial. Dr. Scher disclosed that he is a consultant to and receives research funding from Medivation. Dr. Vogelzang disclosed relationships with numerous companies. Dr. Kibel reported that he is a consultant to Dendreon and Sanofi-Aventis.