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Adding abiraterone after enzalutamide fails does not help enzalutamide responders


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Adding abiraterone after enzalutamide fails does not help enzalutamide responders

Jim Marshall (not a doctor) said ...

In short

Enzalutamide can be given before chemotherapy.

For some men it works to hold their PSA.

But eventually it stops working.

Doctors wondered if adding abiraterone to the mix at this stage would help.

It did not.


More detail

Enzalutamide can be given before or after chemotherapy with docetaxel.

This study looked at men who were having enzalutamide before docetaxel chemotherapy.

Men whose PSA had not risen at week 21 were called responders.

When these responders did later have their PSA rise, half had abiraterone added, half didn't.

There was no difference between the two groups

... end Jim




Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO (ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design.

Patients and Methods

In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression (≥ 25% increase and ≥ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two.


Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group.


Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.

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The foregoing article discusses adding abiraterone to enzalutamide when enzalutamide is showing failure.


Interestingly, if abiraterone acetate (AA) is prescribed separately apart from adding to enzalutamide following enzalutamide failure – and if chemotherapy had not yet been administered - this paper in 2016 remarked that AA was at least modestly effective in PSA response.  Also, the progression-free survival (PFS) and overall survival (OS) with subsequent AA following enzalutamide failure was comparable to that of the earlier enzalutamide.




Unfortunately, the length of effectiveness with abiraterone replacing enzalutamide appears to be measured in few rather than lengthy months.

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Interesting thanks Chuck.  In my case I was on an abiraterone (plus or minus apelutimide) trial, and the abiraterone lasted two years before a spectacular failure which resulted in multiple new bone and lymph mets.  They then tried enzalutimide, but it had no effect on PSa and only made me sick.  I am currently receiving docetaxel, which seems to be working so far - 6 doses.  PSMA PET scan in two weeks should tell.

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Certainly wishing you success with docetaxel.  Possibly enzalutamide or abiraterone might work again following completion of the docetaxel series.  Otherwise, it appears cabazitaxel/Jevtana may be the next medication to which to move.

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