Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer

[pjoshea13]

New international study, below [1].

"Secondary analysis of COU-AA-301 and COU-AA-302" [2] & [3].

Objective: To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS {overall survival} and PSA-RR {prostate specific antigen response rate}.

Conclusion: Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP.

{Gets a bit muddy when you read the Results section below.}

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/355...

Eur J Cancer

. 2022 May 11;S0959-8049(22)00205-2. doi: 10.1016/j.ejca.2022.03.042. Online ahead of print.

Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302

Brooke E Wilson 1 , Andrew J Armstrong 2 , Johann de Bono 3 , Cora N Sternberg 4 , Charles J Ryan 5 , Howard I Scher 6 , Matthew R Smith 7 , Dana Rathkopf 8 , Christopher J Logothetis 9 , Kim N Chi 10 , Robert J Jones 11 , Fred Saad 12 , Peter De Porre 13 , NamPhuong Tran 14 , Peter Hu 15 , Silke Gillessen 16 , Joan Carles 17 , Karim Fizazi 18 , Anthony M Joshua 19

Affiliations collapse

Affiliations

1 Princess Margaret Cancer Centre, Toronto, Canada; Faculty of Medicine, University of New South Wales, Kensington, Australia; Kinghorn Cancer Centre, St Vincents Hospital, Darlinghurst, Sydney, Australia.

2 Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham NC, USA.

3 The Institute of Cancer Research and Royal Marsden Hospital, London, UK.

4 Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY 10021, USA.

5 Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.

6 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

7 Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA.

8 Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY USA.

9 Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

10 BC Cancer, Vancouver, Canada.

11 Institute of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK.

12 Department of Urology, University of Montreal Hospital Center, Montreal, Quebec, Canada.

13 Janssen R&D, Beerse, Belgium.

14 Janssen R&D, Los Angeles, CA, USA.

15 Janssen LLC. Raritan, New Jersey, USA.

16 Institute of Oncology of Southern Switzerland, Bellinzona, Switzerland and Università Della Svizzera Italiana, Lugano, Switzerland and University of Manchester, UK.

17 Vall D'Hebron Institute of Oncology, Vall D'Hebron University Hospital, Barcelona, Spain.

18 Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.

19 Princess Margaret Cancer Centre, Toronto, Canada; Faculty of Medicine, University of New South Wales, Kensington, Australia; Kinghorn Cancer Centre, St Vincents Hospital, Darlinghurst, Sydney, Australia. Electronic address: [e-mail].

PMID: 35568679 DOI: 10.1016/j.ejca.2022.03.042

Abstract

Background: The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear.

Objective: To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR.

Design, setting and participant: COU-AA-301 and COU-AA-302 patients were stratified by metformin and statin use. Cox proportional hazards models were used to estimate hazards ratio (HR) stratified by concomitant medications, and a random effects model was used to pool HR. We compared PSA-RR using Chi χ2 test.

Results: In COU-AA-301-AAP, metformin was associated with improved PSA-RR (41.1% versus 28.6%) but not prolonged OS. In COU-AA-301-placebo-P, there was no association between metformin and prolonged OS or PSA-RR. In COU-AA-302-AAP, metformin was associated with prolonged OS (adjHR 0.69, 95% CI 0.48-0.98) and improved PSA-RR (72.7% versus 60.0%). In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66, 95% CI 0.47-0.93). In pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77, 95% CI 0.62-0.95).In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76, 95% CI 0.62-0.93), while there was no difference in COU-AA-301-P. There was no association with statins and OS in either COU-AA-302 groups. When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78, 95% CI 0.68-0.88).

Conclusion: Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP.

Keywords: Abiraterone acetate; Metastatic castration-resistant prostate cancer; Metformin; Statins.

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

[2] clinicaltrials.gov/ct2/show...

[3] clinicaltrials.gov/ct2/show...

[cigafred]

Nice find, although it took you a whole four days to spot it. You must have taken a couple of days off.

[pjoshea13 in reply to cigafred]

LOL. I'll admit to laziness. I wait for the gnomes at the National Library of Medicine to update PuBMed. Currently 255,379 results for a search on "prostate". Luckily, one can sort by "most recent".

When I started out, it took very little effort to read all there was on a topic (such as PCa + vitamin D - now 1,485 results).

I suppose that the exponential growth of PCa research owes something to demographics. Non-smoking Baby Boomers who are not dying of lung cancer before PCa is found.

Best, -Patrick

[6357axbz]

Conclusions state, “particularly in combination with AAP”.

Did they mean ADT?

[Hidden in reply to 6357axbz]

Abiraterone Acetate (Zytiga) with prednisone or prednisolone.

[6357axbz in reply to Hidden]

Thanks

[GP24]

An impressive list of excellent authors.

[MateoBeach]

Massage the mud enough and, just possibly, a lilly appears to sprout.

[cigafred in reply to MateoBeach]

At this rate this forum will rival Shakespeare. I'm being outclassed.

[Bigm789]

ncbi.nlm.nih.gov/pmc/articl...

Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

[meowlicious99]

If you have type 2 diabetes with PC, is it a nobrainer to be on metformin ?

[pjoshea13 in reply to meowlicious99]

[1] "Overall survival was lower in T2DM patients not treated with metformin.

[2] "Increased cumulative duration of metformin exposure after PC diagnosis was associated with decreases in both all-cause and PC-specific mortality among diabetic men. "

[3] "Our results suggest that metformin may improve outcomes in PCa patients with concurrent T2D."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/327...

[2] pubmed.ncbi.nlm.nih.gov/239...

[3] pubmed.ncbi.nlm.nih.gov/256...

[meowlicious99 in reply to pjoshea13]

endo put my dad on acarbose for T2D. seems like it should be switched out to metformin?