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Advanced Prostate Cancer
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SPARTAN (Apalutamide)

The Apalutamide study presented in SF recently was published in the NEJM yesterday [1]. The comparable Xtandi study paper is still in peer review. Score one for Apalutamide.

The NEJM link is to the full text. I expect that some will be interested in the details.

Others might prefer the NY Times story [2].

"Dr. Sartor and others noted that another androgen receptor inhibitor, abiraterone, which is used to treat cancer once it metastasizes and is also produced by Janssen, is likely to go off-patent soon and will become much cheaper because generic versions will be produced."

Note that Abiraterone Acetate (Zytiga) is a steroidal CYP17A1 inhibitor - not a direct androgen receptor [AR] inhibitor. The confusion is probably due to the fact that hormonal therapy in all its forms ultimately targets AR.

-Patrick

[1] nejm.org/doi/full/10.1056/N...

[2] nytimes.com/2018/02/08/heal...

7 Replies
oldestnewest

Thanks. I was on track to get into my doctor’s planned apalutamide study (NCT02811809), but so far this trial is stalled and have not taken any participants. It seemed that this latest generation of anti-androgen seemed to have merit.

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Link to the Amato study:

clinicaltrials.gov/ct2/show...

Not yet recruiting. Trial was first posted in June 2016!

-Patrick

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The level of cross resistance for Apalutimide (as well as Darolutimide which is in trials Phase III now) following Enzalutimide and Abiraterone (Zytiga) will be interestin. Enza and Zytiga have high cross resistance patterns. A lesser overlay for either of the newer anti-androgens would be a major breakthrough.

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With basic ADT & each of the add-on hormonal drugs, resistance often shows itself as changes to the androgen receptor [AR]. Lupron, Enzalutimide and Abiraterone have different targets, but the weakness of the current approach is that AR remains the ultimate target. Hence the risk of cross-resistance.

In a panel discussion last year, Professor Johann de Bono of the Royal Marsden, worried that, in spite of the success of the newer drugs, we are ill-prepared for the management of PCa that has become resistant to those drugs.

This resonated with me because, 14 years ago, when men were still being rushed into Lupron, I worried about resistance occurring before I was 60, leaving me with more aggressive disease.

Many of us are aware of the AR splice variant AR-V7, that commonly emerges during Xtandi/Zytiga resistance. It's a functional AR that does not need androgen for activation.

However, it's encouraging to read that an:

"... advantage is that darolutamide has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently identified clinically-relevant F876L mutation that produces resistance to enzalutamide and apalutamide." [1]

From 2013 [2]: "A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509." ARN-509 is Apalutamide.

-Patrick

[1] en.wikipedia.org/wiki/Darol...

[2] ncbi.nlm.nih.gov/pubmed/237...

2 likes
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Which trial is this

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Suziq, this is probably the Darolutamide Trial.

"ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer (ARASENS)"

clinicaltrials.gov/ct2/show...

Charles

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Seems that darolutamide is the superior drug with amp. 2Nd and extanti 3rd. Keeping mu eye on these drugs. Thanks patrick. Rocco

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