Extending OS on initial ADT for men with mHSPC

Back in 1989, the SWOG 8494 trial first showed that adding an antiandrogen (flutamide) to bilateral medical orchiectomy with an LHRH agonist (leuprolide acetate) extended median overall survival (OS) by 7 months in newly diagnosed men with metastatic, hormone-sensitive prostate cancer (mHSPC).A later and larger study (SWOG 8894) failed to confirm this initial result, showing that OS was 29.9 months for men treated by bilateral orchiectomy alone and 33.5 months for the men treated with bilateral orchiectomy + flutamide. However, the baseline standard had been set for the effectiveness of standard androgen deprivation therapy (ADT) at a median OS of about 30 months (2.5 years), regardless of how the patients were treated after ADT had failed..

Over the years, as newer drugs have come to market, we have increasingly seen the median OS of men initially diagnosed with mHSPC and initially treated with ADT alone rise with the addition of these new drugs. However, the latest data from the SWOG 1216 trial of ADT + TAK-700 versus ADT + bicalutamide appear to have set a new standard for the median OS of the men initially treated only with ADT + bicalutamide.

As announced at the recent annual meeting of ASCO, in this trial, men with mHSPC treated with only ADT + bicalutamide had a median OS of 70.2 months (just under 6 years) as compared to the men treated initially with ADT + TAK-700 (81.1 months). The authors believe that this extension in OS was largely driven by subsequent treatment with one or more of the many newer, second-line forms of therapy that were approved or available in clinical trials after the 2012 initiation of the SWOG 1216 trial. This might include drugs like abiraterone acetate (Zytriga), enzalutamide (Xtandi), Xofigo (radium-223 acetate) and others.

Now we should be clear that part of this increase in OS may be driven by better ways to identify mHSPC a little earlier in the evolution of advanced prostate cancer, but it was also 16 months longer than had been estimated by the study authors at time of initial development of the SWOG 1216 trial.

The reasonable conclusion is that whereas — in the 1990s — a man initially diagnosed with mHSPC might expect to live for an average of about 2.5 years, today he can have a reasonable expectation of living for close to another 7 years.

This is by no means the long-term survival we would like to be able to achiver, but it does show the progress we have been making.

Unfortunately for the developers of TAK-700, however, the results of the SWOG 1216 trial did not establish a sufficient survival benefit for the approval of this agent. But there are many more agents in development for the treatment of advanced forms of prostate cancer today that there were back in 2012, so hopefully we will soon find a new class of drugs that can — once again — substantially change the long-term of survival of men initially diagnosed with mHSPC.

One Response

  1. This just puts in perspective what we faced 10 years ago and the enormous progress made. It truly does make one wonder if PCA will one day be treated as another chronic illness except for the small subset of men who have such lethal forms at an early age. I never dreamed of living to 80 when diagnosed at 56.

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