Before I get into the meat of today’s post about enzalutamide, I want to briefly make some personal comments about my absence from this blog. As I had mentioned I have been diagnosed with a fifth primary cancer, appendiceal cancer. It is a rare cancer, which required my having to remove my appendix, a piece of my right colon, have an exploratory of my entire peritoneal sack and then what is called HIPEC chemotherapy. The surgery and chemotherapy were rough and came with an extended recovery. I am now at the point in my recovery that I am feeling able to again post to the blog as well as pick up my other Malecare responsibilities. I hope to again continue regular updates. I missed everyone and am very glad to return.

Now to the important work, TODAY’S POST:

Medivation, Inc. and Astellas Pharma Inc. today announced additional data from their Phase 2 TERRAIN trial of enzalutamide (Xtandi) compared to bicalutamide (Casodex) in metastatic castration-resistant prostate cancer (mCRPC), as well as an updated overall survival analysis from the placebo-controlled Phase 3 PREVAIL trial of enzalutamide in chemotherapy-naive metastatic CRPC.

The data from these two trials was presented during a plenary session at the 2015 European Association of Urology (EAU) Congress in Madrid.

The data from the phase 2 TERRAIN trial derived from 375 men with castrate resistant prostate cancer from both North America and Europe. All men had metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue (Lupron, Zoladex, etc.) therapy or following surgical castration.

The primary endpoint of the trial was progression-free survival (PFS) as confirmed by radiographic progression, a skeletal-related event, initiation of new anti-neoplastic therapy or by the subject’s death.

The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus bicalutamide at a dose of 50 mg taken once daily, the FDA approved dose in combination with an LHRH analogue.

The study achieved its primary objective of a statistically significant increase in PFS for enzalutamide compared to bicalutamide. The median PFS in the enzalutamide arm was 9.9 months longer compared to that in the bicalutamide arm (15.7 vs. 5.8 months, respectively).

The median time to PSA progression was 13.6 months longer with enzalutamide (19.4 months) relative to bicalutamide treatment (5.8 months).

Eighty two percent (82%) of enzalutamide-treated men achieved = 50% PSA reduction from baseline by week 13 vs. 21% of bicalutamide-treated men.

The median time on enzalutamide treatment was 11.7 months compared to 5.8 months on bicalutamide.

Also released was additional data from the important Phase 3 PREVAIL trial which was a randomized, double-blind, placebo-controlled, multi-national trial, enrolling 1,717 men from the United States, Canada, Europe, Australia, Russia, Israel and Asia.

This trial enrolled men who were chemotherapy-naïve (not yet had chemotherapy) who also had metastatic prostate cancer whose disease progressed on androgen deprivation therapy (i.e., a LHRH therapy or after bilateral orchiectomy) (mCRPC). This trial provided the FDA the data that led to the approval of enzalutamide at the pre-chemotherapy stage of the disease.

The co-primary endpoints of this trial were overall survival (OS) and radiographic PFS. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus placebo.

An updated overall survival analysis was conducted at 784 deaths and found a statistically significant overall survival benefit with a 23% reduction in risk of death and a 4-month improvement in median survival with enzalutamide (35.3 months

[95% CI 32.2 – not yet reached]) over placebo (31.3 months [95% CI 28.8 – 34.2]).

As of the June 2014 cut-off date of the trial with a median follow-up duration of 31 months: fifty two percent (52%) of the men receiving enzalutamide and eighty one percent (81%) of men receiving a placebo received one (1) subsequent life-extending prostate cancer therapy.

According to Bertrand Tombal, M.D., Ph.D., professor and chairman, Department of Urology, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium, “This study demonstrates that starting patients on enzalutamide at the point when their castration-resistant prostate cancer becomes metastatic has the potential to prolong survival.”

Both of these additional data points confirm that over both placebo and bicalutamide enzalutamide is superior. What this data doesn’t tell us is how enzalutamide would perform under the following circumstances:

1- How it compares to using Abiraterone (Zytiga).
2- How it compares to using it earlier (in the castrate sensitive man) along with other hormone therapies or alone.
3- How it compares with combining it with Abiraterone.
4- How the dose of bicalutamide of 150mg as is commonly used in the UK would hold up against enzalutamide.

It is good news that these data continue to support the use of enzalutamide (Xtandi), but we call on Medivation and Astellas to expand their research to answer the above-mentioned concerns.

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