Abiraterone after Docetaxel for mCSPC?

[john205]

It's been a while since I posted. I am 68 years old, otherwise healthy and now 14 months post-diagnosis with high burden castrate sensitive metastatic prostate cancer (mCSPC), with at least 12 bone mets. On Lupron since the beginning. I completed 6 cycles of docetaxel, the last in January 2018. My PSA dropped from 148 to a low of 0.16 in May, 0.18 in early July, and 0.20 in late August 2019. Bone scan went from hot to cold. My oncologist considers the recent rise of PSA insignificant, and that I am still hormone sensitive. He recommends that I continue to monitor my status until something significant happens, like I become castrate resistant, or until there is more support for further intervention, while hormone sensitive, from ongoing studies.

- I see that Tall Allen suggested abiraterone for golfer1234 with high burden metastatic castrate sensitive prostate CA (mCSPC), following docetaxel. What study is the basis for that recommendation?

- I have seen that enzalutamide (AFFIRM study) and apalutamide (TITAN study) extend overall survival for high burden castrate sensitive prostate cancer, but not for men like me who have already had docetaxel, but the data was limited for those subgroups.

- For high burden metastatic castrate sensitive disease after docetaxel the ARCHES study showed progression free survival but overall survival data are not yet "mature".

Any suggestions for next steps? Thanks

[Hidden]

I was the same situation and 3 different doctors wouldn't give me Abiraterone after Docetaxel until I became castrate resistant. They all felt the additional toxicity and potential side effects was not worth it for something that hasn't been proven.

Zytiga has been proven to extend time to progression and lengthen overall survival when taken early before CRPC, but it hasn't been proven to add anything after early chemotherapy. That was the argument of these doctors.

I just spoke with yet another doctor this week who said the same thing. I know there a lot of people taking Abi in the hormone sensitive phase after Docetaxel, I just wanted to relay what 4 Medical Oncolgists have told me.

[john205 in reply to Hidden]

Thanks Gregg. I had similar conversations with 3 oncologists.

[Hidden in reply to john205]

What did they say?

[john205 in reply to Hidden]

Same as yours.

[tom67inMA in reply to john205]

I've only been to one oncologist and he gave me Abiraterone after docetaxel. It's made my PSA undetectable, and side effects are tolerable. Actually, I blame the side effects more on xgeva.

I think it's worth a try if you can get it, but don't drive yourself crazy in the process.

[Hidden in reply to tom67inMA]

I think the bottom line is a lot of doctors don't want to stick their necks out with something outside the proven studies. I do think the attitude is changing on this although I just talked to yet another doctor who won't do Zytiga after chemo in the hormone sensitive space.

When I had finished chemo, Zytiga for MHSPC had only been approved for 2 months so I think there was more resistance then.

[lynnedrum in reply to tom67inMA]

Why are you on Xgeva?

[tom67inMA in reply to lynnedrum]

Bone mets. Before diagnosis I cracked a rib leaning over the edge of the bathtub cleaning out a hair clog.

[Cheerr in reply to Hidden]

Hi Gregg,

Did you finally take Abiraterone post chemo while being harmone sensitive ?

[Hidden in reply to Cheerr]

No, I had three different doctors tell me they wouldn't prescribe it because it hasn't been proven. So I waited until castrate resistance. Unfortunately, that was only around 6 months after chemo anyway.

[Cheerr in reply to Hidden]

Hi gregg,

Do you think the early chemo while you were harmone sensitive proved beneficial then?

I understand you got 6 months post chemo until castrate resistant. But did the chemo knock down a lot of disease burden / mets atleast?

[Hidden in reply to Cheerr]

I think it did help. One thing I like about the early chemo is that it kills the full spectrum of cancer cells, not just hormone sensitive ones. I don't think you necessarily see the benefit until later. My time to castrate resistance was a little on the short side of average (just under a year), but my PSA dropped to undectable for a year now on Zytiga.

One thing to note about early chemo, the guys it helped most were the ones who were worst off to begin with. They had the biggest improvement with chemo, but also a shorter OS to begin with. So yes I'm hoping that it helped me, but I also know I was in fairly bad shape to begin with.

[Magnus1964]

That is great response from chemotherapy. You have a low PSA. At this point I would go on ADT treatment. You have several drugs to choose from.

[john205 in reply to Magnus1964]

I have been on ADT since the beginning. There are lots of options when resistance occurs. My cancer is BRCA positive which may add options later, also. My question is about what else to do before I become resistant.

[Tall_Allen]

I don't have definitive data (see below). But my reasoning is that Zytiga and Taxotere have different modes of action, and for polymetastatic hormone-sensitive men, we know they both extend life more (and progression-free survival is longer) when used earlier. You will also incur less toxicity when used earlier. I also reason that because docetaxel may reverse AR-V7 in at least some men, Zytiga may work longer if taken immediately after docetaxel (and before the genomics have degraded). Until the optimal timing for sequencing them (or concurrently as Schwah is doing) is known, what advantage is there in waiting?

In the TITAN trial of apalutamide for mHSPC, the benefit of early use was seen in all subgroups, including the 11% who had received prior docetaxel.

In the ENZAMET trial of enzalutamide for mHSPC, there was no additional survival benefit in men who also received docetaxel in the 3 years of f/u. However, in the ARCHES trial, radiographic progression-free survival doubled among men who had already had docetaxel. In the AFFIRM trial for mCRPC, adding enzalutamide after docetaxel increased survival significantly.

Similarly, Zytiga after docetaxel for mCRPC increased survival significantly.

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

[Tonyliv]

Your oncologist is right; they are pretty insignificant numbers. But keep an eye on the doubling rate. I have extensive bone mets and after my six docetaxel sessions my psa nadir was 0.26. I was on degarelix at the time and got a four weekly blood test. (Before I changed to a 12 weekly shot) The results were 0.31, 0.27, 0.28, 0.30, 0.32, 0.34, and then they started to run away. Next two jumped to 0.40 and 0.57, castrate resistance could be argued, and I didn’t want it to run away. I went on abiraterone eight months a go and am bumping along on 0.04. The side effects are tolerable - apart from fatigue, but I regard it as a price well worth paying.

[Dostoevsky]

Evidentiary research rules. Good work my brother: I’m 69 in the same bag as you. Fair seas and following winds.

[dougnola]

There are those far more knowledgeable than me here. My summary is on my bio, but, starting in 12/16 w psa 500, my doc gave me aberaterone w lupron while still very castrate resistant in 7/17 after I finished taxotere/carboplatin combo 1-6/17. My psa was below 0.2 all of 7/17-7/18, decreasing a smidge every month. Hit ND 8/18 and still there as of last week. In essence, virtually no psa for more than 2 years now. All I can say is that it worked for me to go in early and I’m grateful. 🙏🏻 ✌️

[FenBenGolf]

Gregg:

I received doetaxel and Lupron combined which was effective for nearly 2 years (no new lesions and those on organs were resolved). Bone tumors still there but weren't growing until the PSA started to rise. It was at 0.07 for most of the two years but started to rise about 6 months ago. After it got to 1.3 or so (and my hip pain returned) they moved to abiraterone acetate (Zytiga). Within 2 weeks or so pain went away and PSA is now down to <0.03. Still getting the 3 month Lupron shots also. Dr. said this was generally good for a year or so. Abiraterone is administered by tablet (4 - 250 mg tablets daily). Expensive but I found the drug was much cheaper through select pharmacies with the Cigna drug supplement plan. FYI I am 71 and was diagnosed with metastatic prostate cancer 2-1/2 years ago. Gleason of 9.