Apalutamide + Abiraterone combo shows good results in Phase III trial

[curious-mind1]

The trial showed a 30% reduction in disease progression or death for people with mCRPC taking the drug combo (22 vs. 16 months) vs. those taking abiraterone (Zytiga) alone:

janssen.com/janssen-present...

This approach seems to make a lot of sense, as it follows the practice of combining different drugs to block as many of the escape pathways that the cancer can use to spread.

Sounds like good news and a new combo treatment option for people with mCRPC.

Art

[pjoshea13]

Art,

Unfortunately, the drugs have the same target: the androgen receptor axis. i.e. they share escape pathways. We need drugs that do not target the AR, but rather the common AR axis escape pathways.

I'm surprised that Apalutamide has add-on benefit to Abi, because Enzalutamide didn't in one study. Abi is pretty good at starving the AR of androgen.

-Patrick

[LearnAll in reply to pjoshea13]

Keep beating testosterone down with combo androgen suppression does not make any logical sense. If testosterone is already very low (less than 20) what more can be accomplished other than more and more side effects and increased risk of conversion to aggressive variants.Like Pjoshea said that we need to get away from AR axis and diversify by finding how to block other pathways ... thus preventing and stopping Androgen resistant variants. I can not agree more.

[curious-mind1 in reply to LearnAll]

This is all true, but I'm pretty sure people who are facing disease progression while on Zytiga, will welcome an additional 6+ months of disease control (or 30% reduction in death over a 54-month period), while other therapies become available...

Art

[Tall_Allen]

Good news! What stands out to me is that it is particularly good for men who have become castrate resistant while still exhibiting high AR activity. Erleada alone is known to reduce AR amplification (which is the most prevalent cause of resistance), so the combination makes sense. What I don't understand from the press release, is what kind of treatment these chemo-naive men had before. Presumably, most progressed to castration-resistance following a recurrence treated with ADT alone. There is a trial combining them in newly recurrent men. I expect the combination works even better earlier.

[GP24]

I wonder if they required Lupron in this trial. The press release of Janssen does not mention it nor the page on clinicaltrials:

clinicaltrials.gov/ct2/show...

However, this information from Janssen mentions: janssenmd.com/erleada/clini...

"Continuous ADT will be used to maintain castrate levels of testosterone (<50 ng/dL)." And in the inclusion criteria: "Surgically or medically castrated, with testosterone levels <50 ng/dL"

So the combination is Lupron, Abiraterone, Prednisone and Apalutamide?

[MateoBeach in reply to GP24]

Anecdotal reports are that abiraterone + P can maintain castrate T levels without leuprolide drugs. But this is not tested in the trials as it is SOC. Interesting that apalutamide adds by inhibiting AR amplification and this may delay CR development. Perhaps apalutamide may come to replace enzalutamide in standard sequencing.

[GP24 in reply to MateoBeach]

I think the control arm should have been Zytiga followed by Apalutamid. Then one would see if the combination of the drugs works better than using them in sequence. I currently doubt that this would have resulted in a significant difference in outcome.

My understanding is that you can choose whether to take Enzalutamide or Apalutamide following Zytiga. Both drugs are FDA approved in this situation.

[MateoBeach in reply to GP24]

Yes the news is that, while enzalutamide in combination with abiraterone is not advantageous, it is looking like abiraterone with apalutamide does provide added benefit. Now to see if leuprolide could be dropped