Does this say abi and Lupron is as good as it gets.

[Papa1]

I can’t get the full text, but the abstract seems to contradict the idea of triplet as better than abi and adt. What did I miss?

jamanetwork.com/journals/ja...

[Magnus1964]

Try this link for the full article,

doi:10.1001/jamaoncol.2022.7762

Magnus

[Papa1 in reply to Magnus1964]

Thanks, but still got me to a paywall. There’s also an editorial, but it cut off before the conclusion, which is also behind a paywall.

[Magnus1964 in reply to Papa1]

I thought it would display the entire article, guess not. Sorry.

[Tall_Allen]

It's just his analysis of different patient populations. In contrast, Fizazi found the following comparing triplets to doublet trials. The only way to know with certainty is if there is a randomized trial, but the data are so convincing, it probably won't happen:

Comparison of PEACE1 triplet to all relevant doublet trials in different patient pops

[Tall_Allen in reply to Tall_Allen]

Also, the most recent analysis of the ARASENS trial found that the triplet with darolutamide+docetaxel+ADT was effective independent of met volume. Here's the abstract:

Background:

In ARASENS (NCT02799602), DARO plus ADT and DOC significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI: 0.57–0.80; P<0.0001) vs placebo (PBO) + ADT + DOC in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC), with similar overall incidences of treatment-emergent adverse events (TEAEs) between groups. The effect of DARO on overall survival (OS) was consistent across prespecified subgroups, including de novo and recurrent disease. For pts with mHSPC, outcomes based on disease volume and risk provide additional information to clinicians.

Methods:

Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or PBO, with ADT + DOC. High-volume disease was defined as visceral metastases and/or ≥4 bone metastases with ≥1 beyond the vertebral column/pelvis (CHAARTED criteria). High-risk disease was defined as ≥2 risk factors: Gleason score ≥8, ≥3 bone lesions, and presence of measurable visceral metastasis (LATITUDE criteria). OS for these subgroups was assessed using an unstratified Cox regression model.

Results:

Of 1305 pts in the full analysis set, 1005 (77%) had high-volume disease, 912 (70%) had high-risk disease, 300 (23%) had low-volume disease, and 393 (30%) had low-risk disease. DARO + ADT + DOC prolonged OS regardless of high- or low-volume disease with HRs of 0.69 and 0.68 vs PBO + DOC + ADT, respectively. OS benefit of DARO vs PBO was also similar for pts with high- or low-risk disease. DARO improved clinically relevant secondary endpoints vs PBO in high/low-volume and risk subgroups, with HRs generally in the range of those observed in the overall population. Incidences of TEAEs were consistent with the overall ARASENS population across subgroups by high/low volume and high/low risk.

Conclusions:

In pts with mHSPC, the benefits of early treatment intensification with DARO + ADT + DOC on OS and key pt-relevant secondary efficacy endpoints vs PBO + ADT + DOC were similar in patients with high- and low-volume as well as high- and low-risk mH+SPC. The favorable safety profile of DARO was reconfirmed in high/low-volume and high/low-risk populations. DARO + ADT + DOC sets a new standard of care for pts with mHSPC.

meetings.asco.org/abstracts...

[tango65]

Perhaps these 2 links may help

urotoday.com/recent-abstrac...

urotoday.com/conference-hig...

Long term results of the Stampede trial with ADT plus abiraterone vs ADT alone showed a median OS of 6.6 years, which is greater than the overall survival for the triple therapies.

[tango65]

This is what info I have about these therapies:

The authors performed a metanalyses of ten RCT including 5,544 patients:

TITAN, ARCHES, STAMPEDE, LATITUDE, ENZAMET, GETUG-AFU15, CHAARTED, STAMPEDE, ARASENS and PEACE-1.

cancertreatmentreviews.com/...

Both triple therapies had a better overall survival than docetaxel plus ADT, but the triple therapies did not have a better OS than abiraterone plus ADT.

Furthermore, a recent publication about the long term results of the Stampede trial indicates that ADT plus Abiraterone has a median overall survival of 6.6 years.

urotoday.com/conference-hig...

The Triple Therapy in the Peace 1 trial had a median overall survival of 5.72 years.

thelancet.com/journals/lanc...

The Triple Therapy in the Arasens trial is not mature yet. There were 63% of the patients alive at 40 months.

urotoday.com/conference-hig...

The Peace 1 and the Arasens trials used mainly ADT plus Docetaxel as control groups. The median overall survival of docetaxel plus ADT in the Chaarted study was 4.9 years, which was the same than in the Arasens trial.

nejm.org/doi/full/10.1056/n...

RCT trial of the triple therapies using abiraterone plus ADT as the control group are needed.

[Papa1]

First of all—Thanks to everyone for responses. Good reading.

BUT, the following seems to say to me that Abiraterone or any of its more recent sister drugs in combination with ADT is equally as effective as any of them with ADT and Doxitaxel.

“Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT

Conclusions and Relevance  

The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.”

Am I having a Lupron brain fart, or what?

[Tall_Allen in reply to Papa1]

What is causing your confusiont is only because you don't understand how to evaluate research - what makes one study more reliable than another. That isn't because of a lack of intelligence, it is only because there is a body of knowledge that has proven over the years to be trustworthy.

[Papa1 in reply to Tall_Allen]

Thanks.