Adding carboplatin to chemotherapy for mCRPC in post-second generation hormone therapy setting: Impact on response and survival

[pjoshea13]

New study below. [1]

"We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival."

"Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively."

"Patients on second HT invariably develop androgen receptor‐indifferent

subtype. It has been hypothesized that this might be due to alterations in prostate cancer cell lineage, and the development of epithelial‐ mesenchymal transition and/or neuroendocrine differentiation. This phenomenon is described as treatment‐induced lineage crisis.

AR‐indifferent variation constitutes the most lethal form of prostate cancer and exists in approximately one‐fifth of CRPC patients. The situation is more complicated with the reported intra and inter cross‐resistance between second HT and taxane chemotherapies."

"Over a follow up duration of 30 months, 73 out of 90 patients in group (A), 21 out of 33 patients in group (B) and 25 out of 27 patients in group (C) died. The 30‐month overall survival rates were 70.7% in group (B) vs 38.9% and 30.3% for group (A) and (C), respectively"

-Patrick

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

Prostate

. 2020 Jul 31. doi: 10.1002/pros.24048. Online ahead of print.

Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes

Mohamed E Ahmed 1 , Jack R Andrews 1 , Jamal Alamiri 1 , Julianna Higa 1 , Rimki Haloi 1 , Manaf Alom 1 , Giovanni Motterle 1 , Vidhu Joshi 1 , Paras H Shah 1 , R Jeffrey Karnes 1 , Eugene Kwon 1

Affiliations expand

PMID: 32735712 DOI: 10.1002/pros.24048

Abstract

Background: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting.

Methods: We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival.

Results: Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Keywords: advanced prostate cancer; cabazitaxel; docetaxel; hormone refractory prostate cancer; second-generation hormone therapy.

© 2020 Wiley Periodicals LLC.

[Hidden]

Thanks for the information. I may end up doing this as my next treatment.

[dockam]

Thank you for the info, I'm on Abiratereone from Jan 2020 and PSA is ticking up - at 4.9(4.3 last month). Hit a nadir of 0.1 in Summer of 2017 after 15 Taxotere sessions in 2015. MO says a PSA doubling of a month would be of concern. He suggested another round of Taxotere, but if I need to maybe we can add Carboplatin.

Mahalo for your research and sage advice

Fight on

Randy

[RJ-MN]

Thank you for this, Patrick. I had not thought to share it, but when I came across it in early June I had already had 3 docetaxel dosings. I get them at a Mayo satellite, but Mayo oncologists do not often talk to Mayo urologists. However, since docetaxel did not seem to be significantly pausing my PSA (it went up 20+ points after my first docetaxel!), my oncologist was willing to add carboplatin to my last 3 dosings (#6 Docetaxel/#3 carboplatin will be Aug. 3). PSA reduced slightly. I'll have Scans in 3 weeks; that will tell a more complete story. I'm hoping for the Outcome Survival benefit even if PSA has not been much affected.

[pjoshea13 in reply to RJ-MN]

Good luck! -Patrick

[Hidden]

Here's a trial that was done adding Carboplatin to Cabazitaxel. I'll be discussing this with my doctor during my upcoming appointment.

thelancet.com/journals/lano...

[6357axbz in reply to Hidden]

Thanks Gregg, please let us know what he says.

[Hidden in reply to 6357axbz]

Will do.

[Hidden in reply to 6357axbz]

I'm thinking my doctor might do what others here are saying. Starting off with just Cabazitaxel and seeing the response, adding the Carboplatin if necessary. I think I might also want the first cycle to be just Cabazitaxel and then see how that goes before adding Carboplatin. Don't want to be a hero if you know what I mean.

[Hidden in reply to 6357axbz]

I did discuss it with my doctor today. He seemed kind of taken aback by the suggestion of just adding Carboplatin without a reason. He said he will wait for a phase 3 trial first before considering adding Carboplatin.

He said that Cabazitaxel and Carboplatin is a tough regimen and he is only using it now with confirmed NEPC or BRCA mutations (although he'd try a PARP inhibitor first for the BRCA).

[monte1111 in reply to Hidden]

I've already got all of those side effects. I don't see a down side here.

[Hidden]

Thanks for sharing this. It is likely my next treatment and then probably a PARP inhibitor.

[Patrick-Turner]

I had Psa 12 before starting Docetaxel, with countless lymph node and bone mets

After 4 shots of chemo, Psa was flat lining at about 45, and chemo deemed to have failed.

A 5th shot confirmed this conclusion.

If I had added Carboplatin added to Docetaxel, theoretically I would have had a 2.6 times better outcome, but because I had a zero good outcome, 2.6 x zero = zero so outcome still may have been zero good, and forcing me and my team of doctors to seek some other way of treating me, which they did, by agreeing with my request for Lu177.

I know very well what the dreadful longer term side effects of only having Docetaxel.

I can only imagine how much worse side effects may be with added Carboplatin.

But of course the combo of Cabazitaxel + Carboplatin may end up being my last form of treatment after Lu177 eventually cannot be used to extend my life any further because there is a limit on how much a man can have.

I see geneticist on 18 July next to see what may be possible with PARP inhibitors if my DNA suggests I'd get a benefit. I'm into my second series of Lu177 shots, with 5th last week after 4 last year, and maybe Ac225 will added to 6th Lu177 to make the targeted nuclear treatment more toxic to my Pca mets which have managed to survive the previous ionising radiation.

I cycled 52km today, a bit less distance than I planned, but over a course with more hills, and in very cold weather. I got 189km for the week, enough to maintain fitness after having Lu177 shot in week before.

I'll see what happens as time goes by,

Patrick Turner.

[V10fanatic]

As my MO said, just keep alive long enough for the next best thing to come along.......