An important update from the phase III PREVAIL study (Xtandi in the pre-chemotherapy stage) was released thsi evening (actually yesterday evening) in advance of a formal presentation this Thursday at ASCO GU. The news is good, no the news is great.

Last November the trial of Xtandi in men with metastatic castrate resistant prostate cancer who were still chemotherapy naive was ended early because of the very significant and positive results.

In the trial the survival benefit favoring Xtandi over placebo started very early in the study, at about four months and continues until the end when the curves finally cross with only four patients remaining alive.

The overall survival hazard ratio is 0.706, translating into a 29% reduction in the risk of death favoring Xtandi over placebo. This was highly statistically significant. At the median, the overall survival benefit favoring Xtandi is 2.2 months over placebo.

So, which drug is superior, Xtandi or Zytiga in the pre-chemo prostate cancer treatment space? Today, we don’t know this answer as the two drugs have not been studied directly against each other.

However, we can compare the survival curves from their respective phase III study:

In the Zytiga trial the survival curve doesn’t start to separate from the control arm until 18 months into the study (in the Xtandi trial the curves separated at 4 months). The hazard ratio for overall survival from the Zytiga study is 0.79, or a 21% reduction in the risk of death, favoring Zytiga over control. This survival result was not statistically significant probably because the study was stopped too early.

The following are the conclusions from the PREVAIL study as they will be presented at the ASCO GU conference this coming Thursday.

In men with metastatic prostate cancer that has progressed while on androgen deprivation therapy:

* Xtandi significantly reduced the risk of death
* Xtandi delayed the progression of metastatic disease
* Xtandi led to meaningful response in soft tissue disease on imaging
* Xtandi significantly delayed the time to initiation of subsequent chemotherapy
* Xtandi, an oral once daily medication was well tolerated over a prolonged period of treatment
* Xtandi added to hormone therapy at progression provides meaningful clinical benefit to men with metastatic prostate cancer

We have every reason to strongly believe that the FDA will approve Xtandi quickly for men who are castrate resistant but have not yet had chemotherapy. In light of yesterday’s post about NICE (UK) reneging on their approval we can hope that this data will encourage them to reconsider their position.

Joel T Nowak, M.A., M.S.W.