Chemo vs Pluvicto study

[gsun]

My friend is going to be in a trial comparing Pluvicto to Docetaxel. My question is why? Docetaxel has been around for so long that I would think they have all the info on it. PFS as well as OS. As well, the study was announced in 2021 so why are they still recruiting?

[Tall_Allen]

Which is the better next therapy for a man with mCRPC who has failed next gen hormone therapy : Docetaxel or Pluvicto?

clinicaltrials.gov/ct2/show...

They need 200 men for the trial who are watched for at least 3 years.

[gsun in reply to Tall_Allen]

That's the trial he will be in. Two of the doctors doing it I know about and they are the best. One is the doctor behind the chemo part and the other is behind the Lut part. Both tops in their fields. But I still don't understand why they need the data on Docetaxel. I'm sure it has been studied a lot.

[Tall_Allen in reply to gsun]

A randomized clinical trial is the only way of reliably comparing one therapy to another. If they relied on historical trials of docetaxel, there would be no way of knowing whether the results were different only because it was from a different group of patients. Randomization is the only way of assuring that both patient groups are nearly identical.

[dhccpa in reply to gsun]

I suppose that until they are compared head to head, many will assume that newer is better, that Pluvicto is better than docetaxel. But some seem to question whether it is in fact better.

[tango65]

Chemo (cabazitaxel) was already compared to pluvicto in a phase 3 RCT (TheraP trial).

The study was done in patients with mCRPC who had failed docetaxel and some have also failed the new anti androgens.

The authors concluded:

"TheraP is the first reported randomised trial comparing

[¹⁷⁷Lu]Lu-PSMA-617 with a standard-of-care therapy. We

found that in men with metastatic castration-resistant

prostate cancer [¹⁷⁷Lu]Lu-PSMA-617 was more active than

cabazitaxel. Furthermore, the frequencies of objective

tumour responses, grade 3–4 adverse events, and scores

for several patient-reported outcomes also favoured

[¹⁷⁷Lu]Lu-PSMA-617"

thelancet.com/journals/lanc...

The study you mentioned will compare docetaxel vs Lu 177 PSMA 617.

I think it will be adequate to say that Lu 177 PSMA is not inferior to chemo in patients with advanced mCRPC who already had docetaxel.

This may be different in a population with less advanced cancer and without previous chemo treatment.

[Brysonal]

I do wonder when a clinical trial will combine them both 3 x Lu-177 and 3 x Docetaxel.

Seems common sense now I’ve done it to hit the PSMA positives with Lu-177 and the Negatives with Docetaxel

They keep saying this cancer is heterogeneous

[treedown in reply to Brysonal]

Good point.

[gsun in reply to Brysonal]

That would be a good trial.

[Gl448 in reply to Brysonal]

Some of my cancer has PMSA+ and PSA- cells.

I’m assuming docetaxel affects both. It will be interesting when I get my post-chemo staging scans to see how those bone metastases have changed.

[Brysonal in reply to Gl448]

Yes my understanding is Docetaxel affects anything that is growing so hits both. However the side effect profile of 6 is worst than 3 according to my onco so 3 x early Lu-177 with low side effects to hit the PSMA positives ( I was avid) followed by 3 Docetaxel to ‘Mop up’ the PSMA negatives plus any remaining positives made sense to me as 3 Docetaxels are better than ) side effect wise

[Gl448 in reply to Brysonal]

I’ve had 4, #3 was by far the worst (so far), but even it wasn’t nearly as bad as I’d anticipated. Even being the worst, #3 was more an annoyance than a major impact on my QOL.

Cheers.

[spencoid2 in reply to Gl448]

If I remember correctly each doxy got worse until maybe no 4. 5 through 7 or 8 had very little side effects, hardly noticed. Probably a bad day or two around day 4-5 but nothing that I would not have had just living.

[Ramp7]

I chose a trial at Dana Farber with LuPSMA177 last year. I was chemo naive.

[gsun in reply to Ramp7]

How are you doing on that?

[Ramp7 in reply to gsun]

Initially I responded very well. PSA dropped from 8.1 to 0.19. Then slowly went up. I went to Johns Hopkins and met with Dr. Denmeade. He said I was a perfect candidate for BAT. I chose to do an adaptive self administered BAT. Purchased propionate T overseas. Needles are easy to obtain. Completed first cycle with positive results. PSA lowered by 50%. So, I'm a responder according to Denmeade. Started second cycle and shall monitor T and PSA. I should add, my Urologist, and two MO's are following my progress. SOC prevents them from totally embracing this approach but they are very curious as this runs it's course.

urotoday.com/video-lectures...

[Hunterfugi1 in reply to Ramp7]

What did your doctor say were the symptoms of a perfect candidate?

[Ramp7 in reply to Hunterfugi1]

Dr. Denmeade said that since I had done Lupron and Zytiga with a rising PSA. That is the criteria I believe he was basing his comments on.

[Hunterfugi1 in reply to Ramp7]

Did having chemo or not matter?

[Ramp7 in reply to Hunterfugi1]

He did not mention anything along those lines. Mostly ADT drugs.

[SViking]

I thought there were less side effects with Lu177?

[Brysonal in reply to SViking]

Lu-177 done early for me had no side effects and meant I could drop the Docetaxel to 3 times rather than 6 as my onco said the side effects are cumulative so no’s 4-6 are the worst. 3 early Lu-177 and 3 early Docetaxel v 6 early Docetaxel is surely worth trialling.

[GreenStreet in reply to Brysonal]

Fully agree. Makes sense to check it out