MDV3100: New Variable in Already Complex Equation?
Hello, I am Dr. Gerald Chodak for Medscape. The management of advanced prostate cancer continues to benefit from new options, which is great for patients, but then we have a new challenge of how to figure out what to do first, second, and third.
MDV3100 is a novel action molecule that interferes with the binding of testosterone to the androgen receptor. It reduces the transfer of the androgen receptor into the nucleus and reduces its binding to the DNA. Randomized studies against placebo in men with hormone-refractory docetaxel-failed therapy showed a 4.8-month difference in survival that resulted in an interim analysis that ended the study.
Where does that leave us, assuming that the US Food and Drug Administration is going to approve the drug, which is most likely? In addition to having second-line chemotherapy after failing docetaxel, we also have abiraterone, and we will soon likely have MDV3100. Which drug should patients receive first? Arguments might be made in favor of MDV3100 because it is used by itself, whereas abiraterone is used in conjunction with prednisone. Some patients may have more difficulty with that combination than with receiving a single drug.
Does one drug work better? That question can’t be answered without a head-to-head trial, something that is logical to consider, the only issue being cost. Ultimately, we would like to know whether these drugs work better in combination because their mechanisms of action are different.
Both abiraterone and MDV3100 are undergoing testing in men prior to chemotherapy. Therein lies the next challenge. We have sipuleucel-T (Provenge®; Dendreon; Seattle, Washington) for men who are failing hormone therapy, and it is conceivable that we may also get abiraterone and MDV3100. Would patients benefit from a combination of those drugs? If not, which drug should patients get first? We know that the Provenge doesn’t allow for an objective measurement of improvement, whereas that is not the case with MDV3100 or abiraterone.
Patients and doctors are going to face a challenge because it is unlikely that we are going to see additional studies in which these drugs are used together. So the issue will become which drug first, and we are likely to have varying opinions about that. We are not likely to get any data in the near future that would help us solve the problem.
It seems that we have good news for patients, and yet at the same time we are faced with added challenges to sort out a sequence of treatment to try and get the best result. Given the different mechanisms of action between MDV3100 and abiraterone, it would be very nice to know whether the benefit is greater by combining the 2 drugs than using either drug alone in sequence. One could argue that a study like that may well be worth doing, provided that funding is available.
At the end of the day, progress continues for patients with advanced prostate cancer, and now we have the next issue about moving these treatments up earlier and maybe deriving even greater benefit. I look forward to your comments. Thank you.
Authors and Disclosures
Author(s)
Gerald Chodak, MD
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Director, Midwest Prostate and Urology Health Center, Michiana Shores, Indiana Disclosure: Gerald Chodak, MD, has disclosed the following relevant financial relationships: |
