Which form of abiraterone?

[pjoshea13]

New study below.

Compared "a novel abiraterone acetate fine particle formulation (AAFP) 500mg plus methylprednisolone vs. the originator AA (OAA) 1000mg plus prednisone"

"Therapeutic equivalence ... based on serum testosterone levels was confirmed in mCRPC patients."

Study involved "Men with progressive mCRPC, receiving gonadotropin-releasing hormone agonist or antagonist therapy, and with a serum testosterone level of <50ng/dl".

"Over 90% of patients in each group achieved absolute testosterone levels of ≤1ng/dl during the study."

"The averaged absolute testosterone levels ≤0.1ng/dl were achieved in 25% of AAFP-treated patients and 17% of OAA-treated patients."

"Both agents led to similar PSA-50 response rates."

"A PSA-50 response was observed in>65% of patients in both groups on days 28, 56, and 84 ..."

-Patrick

ncbi.nlm.nih.gov/pubmed/291...

Urol Oncol. 2017 Nov 14. pii: S1078-1439(17)30555-0. doi: 10.1016/j.urolonc.2017.10.018. [Epub ahead of print]

Randomized phase 2 therapeutic equivalence study of abiraterone acetate fine particle formulation vs. originator abiraterone acetate in patients with metastatic castration-resistant prostate cancer: The STAAR study.

Stein CA1, Levin R2, Given R3, Higano CS4, Nemeth P5, Bosch B6, Chapas-Reed J6, Dreicer R7.

Author information

Abstract

BACKGROUND:

This multicenter, randomized, open-label, active-controlled study evaluated therapeutic equivalence, steady-state pharmacokinetics, and safety of a novel abiraterone acetate fine particle formulation (AAFP) 500mg plus methylprednisolone vs. the originator AA (OAA) 1000mg plus prednisone in men with metastatic castrate-resistant prostate cancer (mCRPC). The primary endpoint was a comparison of average of serum testosterone levels on treatment days 9 and 10 between groups.

METHODS:

Men with progressive mCRPC, receiving gonadotropin-releasing hormone agonist or antagonist therapy, and with a serum testosterone level of <50ng/dl were randomized 1:1 to either AAFP 500mg daily plus 4mg methylprednisolone orally twice daily (BID), or OAA 1000mg daily plus 5mg prednisone BID for 84 days. Serum testosterone, serum prostate-specific antigen (PSA), steady-state (trough) abiraterone pharmacokinetics, and safety were evaluated.

RESULTS:

Fifty-three patients were enrolled (n = 24, AAFP; n = 29, OAA). Mean age was 75.1 years and 54.7% had Gleason>7. Over 90% of patients in each group achieved absolute testosterone levels of ≤1ng/dl during the study. The averaged absolute testosterone levels ≤0.1ng/dl were achieved in 25% of AAFP-treated patients and 17% of OAA-treated patients. A PSA-50 response was observed in>65% of patients in both groups on days 28, 56, and 84 (P = NS, all timepoints). Days 9 and 10 averaged rounded-up least squares (LS) mean (SE) serum testosterone levels were comparable (1.05ng/dl [0.04], AAFP; 1.02ng/dl [0.03], OAA; P = 0.4703 for LS mean difference). The geometric mean ratio between groups was 1.021 (90% CI: 0.965-1.081); the 90% CI fell within 80.0% to 125.0% equivalence limits. The LS mean differences in abiraterone trough plasma concentrations were not statistically significant at any visit. Adverse event frequency was comparable between arms (75.0%, AAFP; 82.8%, OAA). Musculoskeletal events were more common among OAA-treated patients (37.9% vs. 12.5%).

CONCLUSION:

Therapeutic equivalence between AAFP 500mg daily and OAA 1000mg daily based on serum testosterone levels was confirmed in mCRPC patients. Both agents led to similar PSA-50 response rates. Abiraterone trough levels were similar between treatments. No new safety concerns were observed.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Abiraterone; CYP17 inhibitor; Metastatic castrate-resistant prostate cancer; Prostate-specific antigen; Testosterone

PMID: 29150328 DOI: 10.1016/j.urolonc.2017.10.018

[BigRich]

Being they are comparable, why choose one over the other?

Rich

[pjoshea13 in reply to BigRich]

Rich,

The more expensive one is better. LOL.

The newer form is half the dose. Is that significant?

The steroid drug is also different - I don't know why.

-Patrick

[BigRich in reply to pjoshea13]

Patrick,

I didn't want to subconsciously color your reply. I thought initially it was cost and the utilization of half the dose of medicine. Thank you, for your continuing efforts to bring us the latest research articles to our attention.

Rich

[TommyTV]

I’ve been 1000mg of Abiraterone plus 5mg Prednisone for the last 6 years, with Zoladex. Cost is of no consequence here in the UK.

Under this regime I have responded extremely well. PSA at dx was just under 600, it’s been less than 0.1 for the last 6 years.

No complaints here🙂

[Neal-Snyder in reply to TommyTV]

Nor should there be. Great response, Tommy!

Neal

[Wings-of-Eagles in reply to TommyTV]

THAT IS A FANTASTIC RESPONSE TO ZYTIGA. I HOPE TO FOLLOW IN YOUR FOOTSTEPS,CURRENTLYI'M RIGHT AT 3 YEARS UNDETECTABLE

[Neal-Snyder]

Hi Patrick,

Is there any reason to suspect that someone whose successful response to abiraterone expired might be better served by trying the new one later on, than by re-trying the same one?

Thanks,

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

The new drug uses finer particles. It's not as though it's conjugated with something that might make a difference. Seems to be merely a bioavailability issue - smaller particles = smaller dose.

-Patrick

[Neal-Snyder in reply to pjoshea13]

Thanks, Patrick. I was eating closer & closer to when I took AA, with labs along the way that didn't change from when I waited 2 hours. This was after taking AA for almost 3 years. When I was ready to move to having both at the same time is when AA failed. I've wondered whether I could have stayed on it longer if I'd been taking it with food. This makes me wonder whether I might get a bigger bang for the buck (not that I'm paying) after giving it a rest during other tx's. But I can understand that it might not be in the cards.

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

Regarding food with AA - particularly fatty meals - brings to mind the 2015 paper [1]. I think that Joel recently warned someone against food, because of the greater bioavailability, which could cause one to exceed safe levels. On the other hand, the study doesn't seem to ring warning bells.

For those paying serious money for AA, reduced dose AA+fatty meals could = big savings.

You mention of drug failure has me thinking. There is still a lot of single threading going on. Use something until it fails & then switch to something new. At each failure, PCa becomes increasingly difficult to treat. What if we switched drugs well before they failed? Might be able to return to them numerous times. Perhaps would delay resistance to all.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/260...

[Neal-Snyder in reply to pjoshea13]

Patrick,

My thought had been that if I hadn't made the move so late, thanks to my MO's scare tactics, AA might still be working. But what you're suggesting is very interesting. Do you know of any MOs who are doing this, or is this your original & possibly life-extending proposal, an idea in need of a clinical trial?

Neal

[Dan59 in reply to Neal-Snyder]

Neal, My MO told me that they had people getting an extra 10 months out of Zytiga by eating with it. I myself took the full dose eating bacon and eggs at the same time, and it did work for a while, My liver numbers remained at low end of normal.

[Neal-Snyder in reply to Dan59]

Wish I'd had an encouraging MO like yours, Dan. Mine held me up for months with scare tactics, before I said I want to do it, but I'll do it in steps & we can watch the numbers. The numbers were unchanged good numbers.