Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer in patients with PSADT <10 months.

[tango65]

Mean overall survival was 67 months.

"Enzalutamide was associated with a delay in the

use of a new subsequent antineoplastic therapy (hazard ratio for the use of any subsequent antineoplastic therapy, 0.29; 95% CI, 0.25 to 0.35) (Fig. S2A).

The median time to first use of new antineoplastic therapy was 66.7 months in the enzalutamide group and 19.1 months in the placebo group. "

sci-hub.tw/https://www.nejm...

[GP24]

I prefer local treatments. "After a median follow-up of 51 months, the 5-year overall survival was superior with stereotactic ablative body radiotherapy (SABR) compared with palliative standard of care (42% vs 18%; P = .006)." practiceupdate.com/C/101811...

[GP24 in reply to GP24]

Here is a study which reports a benefit when treating metastases in CRPC:

sciencedirect.com/science/a...

[Schwah in reply to GP24]

I hope to see Tall Allen chime in here. To date he has been reluctant to acknowledge treatment of mets as life prolonging. This study seems to indicate it does.

Schwah

[GP24 in reply to Schwah]

Schwah,

in the conclusion, the second study I mentioned does not refer to overall survival because the study is not designed to make a definite answer on this question. The authors write:

"MDT [metastasis-directed therapy] appears to have favorable clinical results, prolongs the efficacy of current systemic therapy, and may improve outcomes over treatment with change in systemic therapies alone."

Regarding overall survival the following result [based on two years!] is mentioned in the study:

"In order to assess the impact of MDT + systemic therapy relative to change in systemic therapy alone, we compared outcomes of 31 patients treated with SABR at Johns Hopkins Hospital with those of a cohort of 52 patients treated at the same institution who received a change in systemic therapy alone at the time of progression."

Based on this comparison they found:

"Two year OS was 90.30% for those treated with MDT and 76.80% for those treated with systemic therapy only (p = 0.46)"

I think the study indicates that adding local therapy, e.g. radiation of the mets, to systemic therapy is likely to improve the clinical outcomes for a patient. So you may add this treatment if you think it may help you.

[pjoshea13]

There is no doubt that Enza will tighten the screws when the treatment target is the AR axis. The downside is that treatment-emergent adaptations involving the AR axis are more difficult to manage than the more familiar AR-adaptations to classic ADT.

So, if we followed the study until all off the men were dead, I would expect the mortality curve to have become steeper than the in placebo arm. I think that we might be unimpressed with overall survival. If you look at chart A, the curves are getting closer to each other & perhaps about to cross over.

I wonder what distinguishes the men who died early from the men who made it past 6 years? There was (oddly) no Enza advantage in the first 18 months, but an 11 month advantage had developed by 5 years. & then the advantage appears to shrink.

-Patrick

[tango65 in reply to pjoshea13]

Thanks for you comments. I totally agree with your comments.

I wonder how long it took to the patients to die when enza failed. The median time to require other therapy was 67 months , the same than the overall survival. I wonder if this means than when enza fails the cancer is very difficult to control.