Docetaxel or Abiraterone in Metastatic Castration-Sensitive Prostate Cancer [mCSPC]

[pjoshea13]

New Canadian study below [1].

"We conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC {Docetaxel} n = 79, ABI {Abiraterone} n = 42)."

"{progression free survival} favored the ABI cohort .., with 78.0% ... of ABI versus 67.1% ... of DOC patients being free of progression at 12 months."

However, "In this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in {overall survival}."

Another study where longer progression free survival did not translate to longer overall survival.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/340...

Front Oncol

. 2021 May 7;11:658331. doi: 10.3389/fonc.2021.658331. eCollection 2021.

Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

Juan Briones 1 , Maira Khan 1 , Amanjot K Sidhu 1 , Liying Zhang 1 , Martin Smoragiewicz 1 2 , Urban Emmenegger 1 2 3 4

Affiliations collapse

Affiliations

1 Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

2 Department of Medicine, University of Toronto, Toronto, ON, Canada.

3 Biological Sciences Research Platform, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

4 Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

PMID: 34026638 PMCID: PMC8138065 DOI: 10.3389/fonc.2021.658331

Abstract

Background: Both Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).

Methods: We conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.

Results: After a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4-91.8%) of ABI versus 67.1% (57.5-78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3-100%) and 92.7% (85.0-100%) in the DOC and ABI groups (p = 0.97), respectively.

Conclusions: In this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.

Keywords: abiraterone (AA); docetaxel (DOC); metastatic castration sensitive prostate cancer (mCSPC); real-world effectiveness; retrospective analysis.

Copyright © 2021 Briones, Khan, Sidhu, Zhang, Smoragiewicz and Emmenegger.

[Hidden]

Even though there isn't a difference in OS, all else being equal I'd pick the one with the greatest PFS.

[Hidden in reply to Hidden]

Me toooooo.

[pjoshea13 in reply to Hidden]

Sure - but my point is that PFS does not predict OS, yet PFS may be reported long before OS is known and will affect decision making. Can PFS be a meaningful standalone endpoint?

The ACIS trial (Apalutamide Plus Abiraterone/Prednisone in Metastatic Prostate Cancer) "met its primary endpoint at 6 months, showing that apalutamide plus abiraterone acetate/prednisone extended radiographic progression-free survival vs abiraterone acetate/prednisone alone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer."

"For the primary efficacy analysis at 6 months, median radiographic progression-free survival was extended by an absolute difference of 6 months in the combination therapy arm: a median of 22.6 months vs 16.8 months, respectively, for a 31% benefit in risk of progression or death favoring the combination (P < .0001). An updated analysis at a median follow-up of 54.8 months showed a 30% difference favoring the combination arm: a median time to radiographic progression-free survival of 24.4 months for the combination vs 16.6 months for abiraterone acetate/prednisone."

Great stuff, but: "Secondary endpoints were similar between the two arms, including overall survival."

ascopost.com/news/february-...

The issue in the case of ACIS-type studies is that the burden of the add-on drug may seem justified based on pfs, but turn out not to be the case.

-Patrick

[MateoBeach]

Well it was retrospective and not randomized so there may have been physical biases in who to assign which treatment intensification drug. And the OS was only evaluated at 12 months. So o would not put too much weight on this.

[LearnAll]

The studies favoring 3 treatment combos do not report how many patients died due to side effects like, High blood pressure, heart ailments,diabetes complications, obesity, and other toxicities to rest of the body . The tubular vision of prostate cancer related death do not tell the whole story.Total deaths , prostate cancer deaths PLUS deaths due to toxic side effects of heavy treatments..togethe will tell the whole story.

Heavier ,continuous ADT also causes almost in 30% the deadly treatment emergent Neuro Endocrine PCa.My point: the treatments should be individualized according to parameters and subtype of each man PCa. Not excessive..not less..just the right amount of treatment.

A: "what was the outcome of our treatment ?"

B: "Sir, treatment was successful...But patient died."

[Hidden in reply to LearnAll]

Also, how was QoL? If a therapy keeps me alive yet hating life, what's the point?

[LearnAll in reply to Hidden]

That's a great point RSH. Living in hell of side effects and suffering will be worse than dying a few months earlier.Thanks for bringing this perspective as no body wants to talk about toxicity and side effects of heavy, continuous treatments...they just want to focus on survival from PCa.

What a narrow view.

[Leader4077]

I think there is research that indicates starting Docetaxel before second line drugs like Zytiga or Xtandi has better results for OS........is that not the case?

[CSHobie]

Thanks for posting this publication, Dr Emmeneger is one of my Oncologists looking after me. He is a knowledgeable Dr.

[tango65]

One has to be careful when reporting preliminary results which has not been published.

The progression free survival for abiraterone plus prednisone and ADT is 4.3 years. (Failure-free survival=period of time to PSA increase, radiographic or clinical progression, or death.).

urotoday.com/conference-hig...

Abiraterone plus docetaxel and ADT has a radiographic progression free survival of 4.5 years.

meetinglibrary.asco.org/rec...

I believe failure free survival is more strict criterium than rPFS since includes PSA progression and deaths. 4.3 vs 4.5 years are very close, to propose that Abiraterone plus ADT plus docetaxel is the new standard of care.

[LearnAll]

I am trying to understand how the large group of PCa patients and their outcome with 3 drug combo can be generalized to everyone with advanced PCa?

Do someone whose PCa responded extremely well just with Lupron inj. and PSA dropped by 99.97 % in first 12 months...All scans crystal clear ...need same 3 drug combo upfront?

If yes, what is the rationale ? Why this man should be subjected to toxic side effects of 3 drug combo ? Can anyone explain ? How can be outcome based on a large group statistics apply to every individual ...like the one mentioned above ?

Its easy to attack someone who insists on a careful analysis of each man with PCa and design most appropriate treatment which is individualized . Just the right amount of treatment.. effective but with minimum possible side effects and least collateral damage to the body.

[Hidden in reply to LearnAll]

I believe you've answered your question many times yourself.You've stated in previous posts that pca is comprised of different types. Many respond to ADT. Some are resistant to ADT and some don't respond at all to ADT. The pca that is resistant to ADT requires additional treatment to lower T even more than what is capable with ADT. At these lower levels, these pca cells becomes susceptible to treatments.

This, I believe is the working theory supporting the multi drug protocols.

Finally. I think the research community has moved past the previous treatment protocol of using a drug to failure before adding second line drugs. The latest RCTs no longer support this approach and insurance companies now readily accept the multi drug treatment as a first line treatment.

So the question really is,

Why are you resistant to accepting the evidence based treatment protocols?

[LearnAll in reply to Hidden]

TomTom 1111, Why? Because my current regimen is working very very well. I have almost zero side effects. T is 455, PSA is 0.9, Prostatic Acid Phosphatase is 0.7, Bone ALP is 10.9, Hb 14.2, Ca 8.9, Albumin 4.1, NLR 1.4, PLR 62, LMR 3.9 , BMI 23 ,CT: Clear, MRI: no sign of active met. Bone density close to what it was before diagnosis. The results can vary from one man to another man. Not every one may respond this way ...But some men do. After stopping Lupron and Zytiga 1 1/2 year ago, my blood pressure has returned to baseline, My blood sugar is normal again. (HbA1C : 5.3) and energy level is as good as it was 10 years ago. Able to work full time.. over 50 hours every week. Walk/Run 5 miles every day.

If hand Gun has killed the bird , why AK 47 is needed ?

The bird is already dead...its just fine. Just watch the bird closely and if any movement happens. .can shoot again. But if a salesman wants to sell AK47..whether one needs it or not...Man..I'm not buying it. Thank you But No... Thank you.

Every Ones PCa has its own shade...It is difficult but the shade can be figured out with detailed analysis of individual's biomarkers, Scan results, histology and clinical behavior of the PCa. I am just sharing my take with friends on this forum.

If some one want to go for the 3 drug combo... I have no objection. I have no agenda..no mission..no profit motive. I wish them good luck.

[Hidden in reply to LearnAll]

I really doubt the shade can be determined by biomarkers. The biomarkers can be used to determine effectiveness of treatments but not for analyzing pca shade itself.

You seem to have the time and interest to devote to look into this topic. That's great. I on the other hand don't so I'm okay with ADT and Zytiga right now. If I was diagnosed M1 I would certainly throw the kitchen sink at it. The RCTs are very convincing for me.

[LearnAll in reply to Hidden]

That,s OK. We all need to make our own decisions. We are all adults and can see what is in our best interest. There are many types of biomarkers..such as Diagnostic, Predictive and Prognostic. Its vast field to master.Individual case analysis is a time consuming, money consuming tedious process. I have spent almost 1800 hours studying this disease. My bedroom is now looking like an old library with piles of research papers going up to the ceiling. And Of Course, wife does not like new look of the bedroom. But she is tolerating this clutter for sake of my wellbeing.

[tango65 in reply to LearnAll]

Look at this article and compare with TA abi plus docetaxwl new “standard of care”

urotoday.com/conference-hig...

[LearnAll in reply to tango65]

Thank you.