More data from the LATITUDE study.

[pjoshea13]

New paper below [1].

"At 6 mo, 40% receiving AAP {abiraterone acetate and prednisone} + ADT and 6.5% receiving PBO {placebo} + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS {radiological progression-free survival} and OS {overall survival}."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/318...

Eur Urol. 2019 Dec 13. pii: S0302-2838(19)30894-2. doi: 10.1016/j.eururo.2019.11.021. [Epub ahead of print]

Correlation of Prostate-specific Antigen Kinetics with Overall Survival and Radiological Progression-free Survival in Metastatic Castration-sensitive Prostate Cancer Treated with Abiraterone Acetate plus Prednisone or Placebos Added to Androgen Deprivation Therapy: Post Hoc Analysis of Phase 3 LATITUDE Study.

Matsubara N1, Chi KN2, Özgüroğlu M3, Rodriguez-Antolin A4, Feyerabend S5, Fein L6, Alekseev BY7, Sulur G8, Protheroe A9, Li S10, Mundle S11, De Porre P12, Tran N8, Fizazi K13.

Author information

1

National Cancer Center Hospital East, Chiba, Japan. Electronic address: [e-mail].

2

BC Cancer Agency, Vancouver, BC, Canada.

3

Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.

4

12 de Octubre University Hospital, Madrid, Spain.

5

Studienpraxis Urologie, Nürtingen, Germany.

6

Instituto de Oncologia de Rosário, Rosário, Argentina.

7

P.A. Hertsen Moscow Cancer Research Institute, Moscow, Russian Federation.

8

Janssen Research & Development, Los Angeles, CA, USA.

9

Oxford University Hospitals Foundation NHS Trust, Oxford, UK.

10

Janssen Research & Development, Spring House, PA, USA.

11

Janssen Research & Development, Raritan, NJ, USA.

12

Janssen Research & Development, Beerse, Belgium.

13

Institut Gustave Roussy, University of Paris Sud, Villejuif, France.

Abstract

BACKGROUND:

LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC).

OBJECTIVE:

To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS).

DESIGN, SETTING, AND PARTICIPANTS:

A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT).

RESULTS AND LIMITATIONS:

AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p <  0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p <  0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS.

CONCLUSIONS:

Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.

PATIENT SUMMARY:

We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.

Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Abiraterone; Metastatic castration-sensitive prostate cancer; Overall survival; Prostate-specific antigen kinetics; Radiological progression-free survival

PMID: 31843335 DOI: 10.1016/j.eururo.2019.11.021

[Danielgreer]

Hi pjoshea13, I tried to access the full article but they wanted $35! Anyway, do you or someone out there know the median rPFS for Abiraterone/prednisone with PSA at 6 mo. <=0.1?

[pjoshea13 in reply to Danielgreer]

Hi Daniel,

I couldn't get to the full text via sci-hub.tw - but it might be accessible soon.

-Patrick

[kainasar in reply to pjoshea13]

FYI - Able to read and download pdf from Science Direct, hope this helps. sciencedirect.com/science/a...

[tom67inMA]

Generally more very impressive evidence for early use of Abiraterone, but this sentence hurt my head "In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively". So, Abiraterone increases my 'risk' of having a larger PSA drop?

[pjoshea13 in reply to tom67inMA]

Tom,

Just to be clear for someone reading your comments:

"(relative risk [RR]: 1.36 and 2.30, respectively; ... for both comparisons vs PBO + ADT"

But it isn't very clear - at least to me.

-Patrick

[tom67inMA in reply to pjoshea13]

Looking at this again, the number that really pops for me is median nadir, 0.09 for Abi+ADT vs 2.36 for placebo+ADT. WOW! ... just WOW!

If I read correctly all subjects had high risk metastatic prostate cancer and half of them in the Abiraterone group went undetectable. Wow.

[LearnAll]

Patrick,

How does this apply in my case. Details: After being on Lupron and Abi for 6 1/2 months, PSA declined by 99.9 % (from 830 to 0.6). (ALP from 191 to 59) T level less than 5. Never had radiation or chemo. No prostate surgery. No symptoms presently.

Please apply my data to current study results and give some idea of prognosis.

Sincerely appreciate you providing such credible and valuable information .

[tom67inMA in reply to LearnAll]

It's very difficult to apply the results from population studies to individuals. Is your PSA still trending down? That would be a very good sign.

But to try to answer your question, you'd be in the PSA90 group, which only had 12% of the risk of death of the non-responders. But that only begs the question "12% of what?" since we don't know the absolute mortality rate or time frame for either group.

My situation is somewhat similar to yours. I figure we have at least a year or two of good health without major chance of recurrence. In 50 years we'll both be dead. In between those two extremes things get a little fuzzy. I figure I'll enjoy the next year out two and then see what my blood work and scans are saying. If only I was only that rationale about this offline

[pjoshea13 in reply to LearnAll]

So many unknowns.

I'm more interested in overall survival than radiological progression-free survival. In 2017, there was a LATITUDE paper [1]:

"After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died)" {out of 1199}, "the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months)".

The cutoff date for [1] was Oct 31, 2016 (as stated in [2]).

Earlier this year, we had the "final" analysis [2]:

"This final analysis (data cutoff Aug 15, 2018) was done after a median follow-up of 51·8 months"

Deaths: "275 [46%] of 597 in the abiraterone acetate plus prednisone group and 343 [57%] of 602 in the placebo group"

"Overall survival was significantly longer in the abiraterone acetate plus prednisone group (median 53·3 months ...) than in the placebo group (36·5 months ...)"

My guess is that you will do a lot better than median. It's clear from your posts that you are highly motivated & interested in ways to improve survival odds (for instance your post on inflammation). I hope we will both be here a long time.

Best, -Patrick

[1] nejm.org/doi/10.1056/NEJMoa...

[2] ncbi.nlm.nih.gov/pubmed/309...

[LearnAll in reply to pjoshea13]

Patrick

Keeping inflammation as low as possible (preferably C Reactive protein near zero) help control progression of prostate cancer. I am convinced from the reading I have done so far that low inflammation slows/stops progression of cancer. I would like to write a good post about inflammation after holidays once I am fully equipped with solid understanding between cancer and inflammation with medical facts and mechanisms.

In the meantime, we need to spread the word among our fellow members to check and keep systemic inflammation as low as possible. My CRP remains at 0.6 at present.

[Cheerr in reply to LearnAll]

Thanks for the info. I’ll get the CRP test done for dad the next time. Looking forward to your thoughts on how to keep the levels at minimum.

Happy holidays!!!

[LearnAll]

Thanks Tom67,

This 99.9 % decline in PSA brings a question in my mind...does this mean..99.9% cancer cells have died and stopped producing PSA. As I still have my prostate untouched, are these some of the normal prostate cells which are releasing a few drops of PSA ? My MO do not see any need for scans yet in view of my clinical progress..

I do see many similarities in your and my case . Your exercise tolerance, functional capacity and lack of significant symptoms are similar to me.

I check my PSA and ALP every 2 weeks and for last 2 months, PSA is between 0.6 and 0.7 but no trend up or down is discernible.

Just like you, sometimes I even forget that I have prostate cancer because I feel so "normal"

And that make me conclude that just like you I might be around for at least a few years hopefully symptom free. The way you are inquisitive and curious and accumulating lot of knowledge about this illness, I am also gobbling a lot of info in order to leave no stone unturned to combat it by multipronged attack. I am throwing a lot of things at prostate cancer in form of anti inflammatory foods, spices, supplements , exercise etc. besides (lupron+Abitaterone+prednisone) Lets hope for the best. ! Best of luck !