A story on the Bloomberg.com web site gives information about a patient with castration-resistant prostate cancer (CRPC) who has had a zero-level PSA for 40 months since starting on a clinical trial of abiraterone actetate in early 2008.
There appear to be some errors in the story as a whole, but what is clear is that Dennis Prestholdt , a patient now aged 67, and who had been on standard therapy for 10 years before becoming castration-resistant, started to take abiraterone actetate as part of a clinical trial in April 2008, under the supervision of Charles Ryan at the University of California San Francisco. “Within two months of starting treatment,” i.e., by June 2008, his PSA had dropped to zero, and it is still at zero some 40 months later.
Mr. Prestholdt would seem to have been enrolled in the Phase I/II trial of abiraterone acetate in men with castration-resistant prostate cancer who were still chemotherapy-naive. It should immediately be pointed out that men in this study did not have to have evidence of metastatic disease.
Now it is probably not reasonable to expect that most men with widespread, metastatic CRPC will have an additional 3 or 4 years survival after becoming castration resistant — even with the benefit of abiraterone therapy. Equally, it is not correct to think that back in 1985 (as suggested in the article) men only lived for 12 months after starting hormone therapy. This looks like a misquote. What Dr. Ryan almost certainly intended to communicate was that in 1985 a man who was failing standard hormone therapy might only expect a further 12 months survival.
Having clarified these points, the experience of Mr. Prestholdt in this Phase I/II trial does appear to suggest that abiraterone may be able to offer a 3- to 4-year survival benefit (or maybe even more) when added to standard hormone therapy in at least some men with non-metastatic, chemotherapy-naive CRPC.
We can presumably expect a Phase III clinical trial of abiraterone acetate in men with non-metastatic, chemotherapy-naive CRPC to be started soon, but it may take until 2017 or 2018 to see the results of such a trial. The Southwest Oncology Group (SWOG) will shortly be starting a Phase II trial of abiraterone acetate in men with a PSA level of > 4 ng/ml after initial androgen deprivation therapy as well. However, a Phase II trial of TAK-700 (orteronel) in men with non-metastatic, chemotherapy-naive CRPC and a rising PSA level was initiated over a year ago (in January 2010). That small trial might show results as early as 2015.
What is quite certain is that the battle to show which of the new second-line hormone therapies for progressive hormone therapy is most effective and can be effectively used early in the onset of castration-resistant prostate cancer is starting to heat up.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment Tagged: | abiraterone, CRPC, orteronel, survival, TAK-700
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So how does this Kaplan-Meier thing work? The final results (click here) show almost no one surviving at at 18 months, though the median was 15.8 months. I need a lot of help understanding that (post chemo).
In the NEJM paper, there is some evidence that abiraterone works better in earlier settings. For example, for the subgroup of patients with baseline ECOG performance status score of 2, there was not much difference in the overall survival (7.3 vs 7.0 months).
However, since the confidence interval (CI) of the hazard ration (HR) for this subgroup is too large to draw a definitive conclusion, we unfortunately will need to wait for the results of the pre-docetaxel trial to understand this better. In the meantime, it seems there is some evidence to suggest that patients should start abiraterone as soon as possible.
I do wonder how the crossovers will affect the overall survival of the pre-chemotherapy trial and when the double-blind gets lifted so that the placebo patients can start the chemo and then abiraterone.
And you were right about the lack of any post-trial therapy discussions.
Sometimes chemotherapy is very helpful to increase the chance of survival. But … it depends on the condition. Second-line chemotherapy is the last hope to increase the survival rate.