According to an announcement earlier today, the U. S. Food and Drug Administration (FDA) has approved an expanded indication for abiraterone acetate (Zytiga®) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), inclusive of patients who have not received any form of chemotherapy.
Obviously, this announcement significantly expands the numbers of patients for whom abiraterone acetate is an approved form of therapy.
This approval is based on data first presented at the ASCO annual meeting earlier this year, and previously discussed at length on this web site.
Happy Holidays seems like an appropriate expression.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: abiraterone, castration-resistant, chemotherapy-naïve, mCRPC, metastatic |
THE "NEW" PROSTATE CANCER INFOLINK 
According to the media release from the FDA, the median overall survival has now been reached in the abiraterone acetate arm (at 35.3 months). That’s quite impressive.
Well … It’s all relative. The median overall survival of the patients in the prednisone + placebo arm was 30.1 months, so the survival benefit was 5.2 months or 5.2/30.1 x 100 = 17.3%. That is certainly nothing to sniff at, but I am tempted to wonder whether the developers were hoping for a better result! It will be interesting to see what the analogous trial of enzalutamide may show.
It has been noted oft-times before that prednisone alone certainly appears to have at least a small survival benefit in the treatment of mCRPC (although exactly how much is unknown). The really impressive thing is that even prednisone + a placebo showed a survival benefit of > 2.5 years in this group of patients with mCRPC.
I think, without crossover, the OS in the control arm would have been lower. It was 27.2 when the trial got unblinded (when the patients were allowed to crossover). However, we will never know the true hazard ratio.
My adjective was for the overall improvement in the absolute sense. What a change from the 21.7 months measured in the Provenge trial just few years ago.
Errr … Was the Happy Holidays for the manufacturers, given the doubts you expressed in this and previous comments on the one and only study? Saw an interesting article in Clinical Oncology the other day, much of which seemed relevant to this drug — “Drug trials: often long on hype, short on gains.”
Thanks for your tireless work over the years — hope you get a bit of a break over the Holidays (if I can use that expression?)
Terry:
For those with mCRPC I think the option of being able to take abiraterone before having to have chemotherapy is a fairly significant advance … even if not life-saving. Hopefully you will never find you need to agree with me.
With respect to the article you mention, I have long been amused by the Janus-like posture of The New England Journal of Medicine, which on the one hand is one of the major publishers of “important” results of trials funded by pharmaceutical companies and whose editors, on the other hand, have long been among the loudest critics of the pharmaceutical industry (which is a key source of funding — through advertising — for the NEJM). It reflects America’s Janus-like posture on so-called “freedom of speech” (which is actually “freedom of speech at any cost, so long as my truth is the accepted one”). I will have a look at the article you refer to later today.
I was a pre-chemotherapy patient who started Zytiga last February and I am still on Zytiga. I think I will make a year out of it and so it was not 5 months, maybe 16 months. I still think it’s one of the best thing out there.
Dear Ralph:
So (as Summer pointed out in the first comment posted above) the median overall survival time of chemotherapy-naive men like you on Zytiga + prednisone in this trial was nearly 3 years. It was the survival benefit compared to a placebo + prednisone that was only 5 months or so. On that basis there is a good reason to think you may well be smiling in the new year in 2014 and 2015 too! (And maybe even longer!)
The median overall survival reached only with the abiraterone acetate was nearly 3 years. I think the standard cure for mCRPC will be now abiraterone, then chemotherapy, then enzalutamide. I wonder if with this approach it’s more correct to think of an OS of more or less 5 years for mCRPC patients.
Dear Fabio:
Many of the men (and perhaps even nearly all of the men) who survived for a median of 3 years after taking abiraterone + prednisone in the trial leading to approval of abiraterone in the chemotherapy-naive setting would have had other forms of therapy after abiraterone + prednisone, but we don’t know exactly what. Thus, at the moment, we can only say that the longest period of known median overall survival after a man is clearly metastatic and castration resistant is 3 years — among men who are asymptomatic or mildly symptomatic at initiation of treatment with abiraterone + prednisone (regardless of any subsequent form of treatment).
Is it possible that some specific sequence or combination of abiraterone acetate, enzalutamide, sipuleucel-T, and chemotherapy might extend that median overall survival period? Yes, clearly it is. However, I don’t think there are any data yet to endorse the idea that the median overall survival after a patient can be defined as having asymptomatic or mildly symptomatic, metastatic, castration-resistant prostate cancer is as long as 5 years.
One aspect of the FDA press release puzzles me.
It seems that the data presented showed a median overall survival of 35.3 months for patients on Zytiga. At the same time, the median radiographic progression-free survival (rPFS) had not been reached.
In my simple understanding, you find the median overall survival when half the patients have died. If half the Zytiga patients have died, mustn’t the rPFS have been reached?
What am I missing?
Grandpa James (and others):
Please see the new article discussing the details of the data that form the basis of the approval of abiraterone acetate for the treatment of chemotherapy-naive mCRPC published today on this site.
Articles are of great interest, since I have just started on Zytiga.