DR BEER: This was an international study of 1,199 men randomized 2 to 1 to the active drug versus placebo.
And the results are fairly compelling, I think. The median survival was 18.4 versus 13.6 months with a hazard ratio of 0.63, so that indicates a 37% improvement in overall survival in these postchemotherapy castration-resistant prostate cancer patients.
And all the other measures of clinical activity and efficacy followed along in the same direction. So PSA decline was seen in 54% of patients treated with enzalutamide, 2% of placebo patients.
Objective response in the soft tissue is 29% versus 4%. Quality-of-life improvement 43% versus 18%. Median time to progression, 8.3 months versus 3.0 months. So really, across the board, no matter what measure we used, this new drug was clearly superior to placebo in this setting.
DR LOVE: What do you see as the clinical implications of this study?
DR BEER: I think it’s a very attractive agent, both from the standpoint of efficacy and from the standpoint of safety. As we look at the safety data on this study, the percentage of patients discontinuing treatment due to an adverse effect was no higher in the drug group than in the placebo group, so a very well-tolerated drug in general.
The one unusual but notable toxicity is seizures, which was reported in 0.6% of patients in this paper — actually 0.9% of patients in the prescribing information that came out with the FDA approval. There were no seizures in the placebo group, so this is a drug where overall tolerability is excellent, but patients who are at risk for seizures, such as patients with brain metastases, are probably not good candidates.
One of the exciting features of this drug and something we discussed earlier is the absence of the need for corticosteroids. So, unlike abiraterone, this drug is dosed by itself. And some of the issues with long-term corticosteroid exposure should not be an issue for patients on this drug.
DR LOVE: So William, I’m curious in terms of the steroids that are used with, for example, abiraterone. I mean, theoretically, this is physiologic replacement. But do you think there’s side effects, toxicities?
DR OH: With corticosteroids? Unfortunately, I think corticosteroids have become the bane of our existence as practitioners taking care of men with prostate cancer. With abiraterone it’s really required, as we talked about, although the extent of requirement is still debated, and there are patients in whom you can cut the dose down and not see secondary side effects. But we’re using it with chemotherapy. It’s part of many of these other regimens really for historical reasons only. And I’ve found that many of my patients really complain about the steroids even when they’re having a very good response, for example, to docetaxel chemotherapy or cabazitaxel chemotherapy. So I’ve tried to avoid steroids when I can. With abiraterone you have to start with prednisone, but in some patients that becomes the more limiting factor.