The Phase III PROSPER trial of enzalutamide + androgen deprivation therapy (ADT) versus a placebo + ADT in men with non-metastatic castration-resistant prostate cancer (nmCRPC) has apparently met its primary endpoint of improved metastasis-free survival.
This announcement was made by Pfizer and Astellas Pharma earlier today in a joint media release. The media release also states that preliminary analysis of safety data from the PROSPER trial is consistent with the safety profile of enzalutamide (Xtandi) in earlier clinical trials. However, …
What we do not have yet are any details about these data. Pfizer and Astellas state only that
Based on the results of PROSPER, the companies intend to discuss the data with global health authorities to potentially support expanding the label for XTANDI to cover all patients with CRPC
and that
We look forward to further analyzing the detailed efficacy and safety results from PROSPER, and submitting them for presentation at an upcoming major medical meeting.
If enzalutamide is approved for an expanded indication based on the data from the PROSPER trial, that approval will be inclusive of treatment, in combination with ADT, of men with nmCRPC, and no other drug has been approved for this indication to date. It is possible that the companies will present the data from the PROSPER trial at the Genitourinary Cancers Symposium early next year — or perhaps even earlier.
The randomized, double-blind, placebo-controlled, Phase III, multi-national PROSPER trial enrolled ~ 1,400 patients from multiple nations who had nmCRPC that had progressed, based on a rising PSA level despite ADT, but who had no symptoms with no prior or present evidence of metastatic disease. The primary endpoint of the trial was metastasis-free survival (MFS) — a measure of the amount of time that passes until a cancer can be radiographically detected as having metastasized to other parts of the body. The trial evaluated enzalutamide at a dose of 160 mg taken orally once daily + ADT, versus placebo + ADT.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: castration-resistant, enzalutamide, nmCRPC, non-metastatic, outcome, PROSPER, trial |
THE "NEW" PROSTATE CANCER INFOLINK 
With this trial favoring enzalutamide + ADT in the non-metastatic CRPC and STAMPEDE results just a few days ago favoring abiraterone + ADT in the hormone-sensitive setting, are there any trials underway that will compare these two, or test whether enza + abi + ADT is better than either enza + ADT or Abi + ADT?
Or do we think the SOC will evolve to abi + ADT in the hormone-sensitive setting and then switch to enza + ADT when castrate resistance develops (knowing that cross-resistance is quite common between abi and enza)?
And now that we have seen evidence that abi + ADT has advantages over docetaxel + ADT, are there trials underway to check abi + docetaxel + adt versus either separately?
Dear Anonymous:
You are asking good questions but good answers may be hard to obtain.
Abiraterone acetate is about to come off patent in the very near future. This makes it unlikely that Johnson & Johnson will be willing to invest any more serious money in clinical trials of this drug because they will put all the available resources into the development of apalutamide (ARN-509). This will affect all sorts of issues related to future trials of drugs in HSPC and CRPC. Furthermore, funding available to the NIH for clinical trials here in the USA has been shrinking for years and the current administration would like to further cut funding to the NIH — although Congress seems to have a somewhat different perspective.
There are certain trials that many physicians and patients might like to be able to do that just never get done because of lack of financial resources, and I haven’t had time to do an exhaustive assessment of all of the ongoing trials that might affect your question. (I still have a full-time job.) On the other hand, I am aware that there is an ongoing trial (Arm J of the STAMPEDE trial) in which patients were randomized to treatment with ADT + abiraterone + enzalutamide as compared to ADT alone. This trial was originally expected to report results in 2015, but I haven’t seem any results as yet.
I think it is probably far to early to determine how things are going to evolve over the next 3 to 5 years with regard to standards of care. For example, the results of the ongoing Prostvac trial could be game-changing, as could the results of the ongoing Phase III trial of apalutamide in nmCRPC.
Thank you. Amazing that Abi is soon to come off patent that it was only approved a few years ago. Will be interesting to see how fast and far the price falls.
I just peeked at clinicaltrials.gov, but no results are posted yet for the PROSPER trial.
Jim:
There won’t be any results posted anywhere until the data analysis is complete, at which point they will get presented at a major medical meeting.
You may recall that Pfizer/Medivation closed out their study early, just a day after the STAMPEDE and LATITUDE abi results at ASCO this past June — so these results were expected.
I realize evidential studies are not yet available, but the buzz amongst the savvy genitourinary medical oncologists appears to be that the introduction of any second-line antiandrogen at time of castrate resistance, metastatic or otherwise, will produce a result. The big question, as asked by “a nonny mouse”, is which is more effective — or are they best in combination? And what about the new drugs coming online? ARN-509, ODM-201, etc., etc.
On another score, I heard reliably that Genomic Health is introducing a commercial AR-V7 test in January. This is long overdue — was originally scheduled for this summer; it will provide an alternative to Hopkins with easier logistics, I am sure.
Parsing this test, it is really an economic issue given that 30% or more men are AR-V7 +ve. I expect the insurance companies will make it a requirement to be AR-V7 -ve before approving abiraterone or enzalutamide. A 1-month supply of either drug is more costly than the test. It may also save a significant patient co-pay, at no cost to the patient.
Thanks for your reply, Sitemaster; I was not clear about the timing of the release of data from trials on the clinical trials.gov site.
Thanks Rick. That makes sense.