ARSI PR wars: Nubeqa (Bayer) vs Erleada (J & J) lawsuit

I recently had to have emergency surgery for a perforated colon due to diverticulitis, was in the hospital for over a week during Thanksgiving . Im so thankful to be alive let alone being able to walk

@northoftheborder
There is some logic to starting with abiraterone.

If you get on abiraterone first It does give you a couple more years at least before you move on to a lutamide. As long as it doesn’t fail you (PSA rises) then moving to a lutamide Extends the amount of total time you can be on an ARPI.

If abiraterone Fails you and you try to move onto a lutamide The odds are not good that it will work, Around 15%.

If you start on a lutamide and it fails you Then you cannot usually move onto to abiraterone.

I got 2.5 years out of abiraterone, and now almost 3 out of Darolutamide. If I had started on a lutamide It very likely would’ve failed me within five years.

Just something more to think about

@jeffmarc I think that thinking might be changing

It's true that if you're going to sequence, it's better to go from Abiraterone to a -lutamide than the other way around (see the 2019 Khalaf trial), but either way, the second drug you sequence to will be much less effective than if you'd started with it: once the cancer finds a way "around" the AR pathway with one drug, it can do the same thing more easily with the next.

So I think the consensus is shifting from "save the best 'til last" to "give it your best shot right away."

Abieraterone is good, but overall for mCSPC, the -lutamides are even better (compare the results of LATITUDE and TITAN for mCSPC, with the usual caveats about numbers from different studies). So I think it made more sense for me to get all of Apalutamide's benefits up front — the Shock and Awe approach — rather than a fraction of them later, when Abiraterone failed.

Obviously, this remains an open discussion among oncologists. In a couple of years the picture should be clearer.

@northoftheborder
If you can switch from abiraterone to a ludamide before Abbie fails it can give more time with ARPI drugs.

And and then there is this from the Lancet About the best way to sequence ARPI drugs
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30688-6/abstract

@jeffmarc Yes, that's the 2019 Khalif study I referenced, confirming your point that if you're going to sequence with mCRPC, it's better to do Abiraterone -> Enzalutamide rather than the other way around.

Unfortunately, it doesn't look at the impact of sequencing on developing castrate resistance in the first place, because the lutamides weren't used yet on-label for mCSPC during the time they collected the study data (AFAIK). Doublet therapy for metastatic castrate-sensitive PCa mainly post-dates that.

@northoftheborder
My understanding is that abiraterone Along with ADT can also delay castrate resistance.

Hey, I don’t really like abiraterone, It gave me a lot of problems, But it also gave me 2 1/2 years before I moved on to Nubeqa.

You may be right though that they did not study this properly because the drugs weren’t available when it was done.

@jeffmarc wrote "My understanding is that abiraterone Along with ADT can also delay castrate resistance."

Yes, you're right. That was the LATITUDE study that I mentioned. The results weren't as dramatic as ADT+Apalutamide in the TITAN study, but they were still a solid improvement over ADT alone.

There have been similar studies showing the benefits of Enzalutamide (ARCHES, ENZAMET) and later, for Darolutamide (ARONOTE) as first-line treatments in doublet therapy for mCSPC, rather than sequencing them later.

All showed stunning improvements, both for overall survival (OS) and progression-free survival. TITAN, for example, failed to reach media OS during its 4½ years — too many patients in the study group insisted on staying alive. 🙂

Caveat: while all the studies required patients to be have mCSPC and not to have taken an ARSI before (I think), they mostly didn't require patients to be newly diagosed. That means that the tine to progression-free survival and overall survival are likely *understated,* since study participants may have had mCSPC already for months before the studies started, and may even have had chemo.

@brianjarvis But you have to ask yourself: Where is the data coming from? Aren’t these tables based on the data that the drug manufacturers are reporting?

@heavyphil The sources in those graphics are listed at the bottom of each. Yes, would be interesting to see if what they’re saying now aligns with the cited studies, or if they’re spinning the narrative.

The old adage has some truth - “Numbers will say anything you want them to if you torture them long enough.”

@brianjarvis Exactly! Actually looking at the data takes time and expertise that most of us don't have.

Those PowerPoint-style slides you shared are "data storytelling" (as we called it in my international-aid work) using carefully-curated key figures, rather than a deep dive into the messy source research and data.

Data storytelling makes the information more accessible for cancer patients — which is a very good thing — but it also introduces the biases of the person or org creating the slides, and removes the key figures from their original contexts (including the researchers' varying goals, methodologies, and caveats). You can tell many different stories using the same data, depending on what you decide to highlight.