Opinions on Lu-PSMA-617 Clinical Trial

[PHnerd]

Hello all, my father’s oncologist has suggested we start looking into clinical trials or chemotherapy now for his metastatic castration resistant prostate cancer (metastasized to the coccyx/pelvic bone in 2019). The trial the oncologist suggested is in the title. Wondering if anyone has gone through this trial or has received Lu-PSMA-617 and what the results were like?

Dad has never had chemotherapy before (only anti-androgen medicines like Zytiga and Xtandi in addition to Zoladex injections and the works). Dad is hesitant to pursue the trial because he really hates the hospital that’s running it (I agree, they have had the worst services in treating my dad which is why we got him moved to a cancer centre closer to home that we’re much happier with). Also, he can pursue chemo at the hospital we’re with now right away, but if he pursues the trial and ends up in the non-experimental group, he’ll have to do his chemotherapy at that other hospital (which is also 30km away, aka very far). My opinion is since he hasn’t pursued chemo yet, we pursue the chemo through our regular cancer centre for now. If that fails or the cancer comes back afterwards, we can proceed with trials and other options (this trial has been around for a while in British Columbia, Canada where we live). Any thoughts or suggestions? We’re really stumped.

PS: I should also mention that a friend’s dad recently did this trial and was in the experimental group. Things were going great until a few months after his last Lu injection, after which everything declined quickly. He got multiple infections and C-diff, and eventually passed away a month back. It’s left a sour taste in my mouth about this (though my friend said her dad had a very different prostate cancer and health history from my dad so that could also be it).

[Tall_Allen]

Many in the US (and on this forum) have had Lu-177-PSMA-617 (called "Pluvicto") without a clinical trial, because it is FDA-approved here. It works great for many. For a minority, it can make matters worse. I believe that everyone taking it should get an FDG PET scan in addition to a PSMA PET scan. But I don't know what options are available in the clinical trial he is contemplating.

prostatecancer.news/2019/12...

[RyderLake2]

Hello,

There is a trial available to men through the BC Cancer Agency called the SPLASH trial which involves receiving Lutetium without chemotherapy. It has several advantages which might appeal to your Dad. First, no chemotherapy. Second, it is a randomized trial rather than a blind trial so you know which arm you are on. Third, it is randomized two to one so 66% chance of receiving the Lutetium vs a 33% chance of getting SOC. Fourth, it allows for a crossover so if your Dad starts failing while in the SOC arm he will be switched to the Lutetium arm. Finally, if in the SOC arm your Dad will be switched from whatever second tier ADT drug he is currently on (e.g. Xtandi) to another (e.g. Zytiga) which is difficult to do in BC. There could be a benefit from having this done. One downside is all treatments have to be done at the BC Cancer Agency at VGH in Vancouver. Good Luck! A fellow west coast Canuck.

[PHnerd in reply to RyderLake2]

Wow, I didn’t know about the SPLASH trial. We’ll definitely give it a look! This trial offers him a 50/50 chance of being in either group and he will be informed which group he will be in. But yes, still a lower chance of getting the Lu.

[RyderLake1 in reply to PHnerd]

Hello,

My contact at the BCCA is Dr. Lucia Nappi. I am not sure where your dad lives (or even if he is close to Vancouver) but my recommendation is is to have your dad's oncologist contact her to discuss eligibility and space availability. As in all clinical trials involving Lutetium your dad has to be PSMA avid (about 80% of men are) and if he is accepted onto the Lutetium-177 arm then a second problem is there is a widespread North American shortage of this radioactive ligand. They have to bring it in from overseas. Let me know what you find out and good luck!

[gsun]

If your Dad is failing on the ADT, in BC, he has to have another treatment first such as chemo or radiation before he can get Lu-177. If he is not failing, he has to keep on it until it does. If this SPLASH trial needs no chemo, bonus! Dr. Phil Cohen (head of nuclear medicine at Lions Gate Hospital) gave a talk to our Advanced Prostate Cancer Support Group last night about the approval of Lu-177. The company trials only showed a four month survival rate with this treatment. Dr. Cohen disagrees on this. I think the trials were hurried. He has been working on isotope therapy for years. The big issue is that the therapy has been approved but not funded. The cost will be around $100,000. That puts it out of my reach for sure. Your Dad should become a member of the support group. Good luck!

[PHnerd in reply to gsun]

So does Dr. Cohen believe the Lu-177 offers better survival time than 4 months? What did you mean by you think the trials were hurried? And do you know of any updates on whether the therapy will soon be funded or not?

I don’t think this is the SPLASH trial that dad will be on because he has a 50/50 chance of being in either group (but it’s still not blinded so he will know which group he will be in, but it’ll be randomized).

[gsun in reply to PHnerd]

Yes, he thinks survival would be longer. Novartis got this to market in about two years. That is not long enough to get accurate data. It just got approved and ,at the cost, I can't see it getting funded for a long time, if ever. Dr. Cohen said there are another dozen isotopes being worked on now and when they start to come out for approval, the cost should come down dramatically. Just hope we can survive that long!

[meowlicious99 in reply to gsun]

Confused about ' 4 month survival ' . Is it 4 month addition compared to SOC. VISION had 5 month benefit. Also OP's father hasn't had chemo.

I am not aware of any data for prechemo lu177 suvival benefits.

[gsun in reply to meowlicious99]

The survival rate was for people who had other treatments and they failed. I don't know what the pre chemo rate is as I have never heard of using it without chemo first.

[PHnerd in reply to gsun]

I guess that’s where my concern is and why I was telling dad it might be better to pursue chemotherapy at the hospital he really loves first? But he’s been on Zytiga and recently was switched to Xtandi. His PSA is low (1.00-2.00) but on the rise slowly. His onc was the one that recommended we see if he’ll be fit for a clinical trial first but it didn’t seem to state that he’d had to have failed chemo first to be eligible (and we just spoke to the research team today too).

He’ll be getting his PSMA scans done soon. I don’t think any FDG scan was ordered (not sure what that is or what it’s for but Tall_Allen mentioned it in his comment above).

[noahware in reply to PHnerd]

The FDG scan would not be a standard order for most of these Lu177 trials... you would probably need to see how it might be paid for, as out-of-pocket might be the only option.

The PSMA scan lets one know if his cancer has enough PSMA to justify trying the Lu177. The FDG scan could show additional areas of cancer that are not PSMA-avid, and that would NOT respond to the Lu177.

By getting one, you would remove some of the uncertainty of chances of success. Otherwise, it's something of a crap shoot. Just because MOST men do well/better does not mean any given individual will.

I am approaching session five in a Lu-177 trial in Boston and while I have been assured repeatedly that my disease is basically "stable," it is disconcerting to learn that I have new areas of uptake on bone scans and a PSA that is on the rise!

Side effects have been minimal, though, and I remain pain-free... which is my primary goal in treatment.

[gsun in reply to noahware]

Did you have an FGD scan?

[noahware in reply to gsun]

No, that was my point: an FDG scan is NOT part of the trail protocol. It is not in the financial interest of Novartis to spend extra money just to possibly rule out men who might not see much benefit from their drug. They will want as many men as possible to pursue that VERY expensive treatment, and it will be up to individual men and their docs to evaluate if they want any additional info an FDG might provide. (But will insurers want to pay for that FDG? I doubt it.)

I could have paid for an FDG scan myself, but I was happy enough to just take my chances. I am only suggesting the FDG scan as a means of being more certain of the potential benefit, based on the input of TallAllen.

[gsun in reply to noahware]

I would think Novartis would benefit from the scan. That way they could cherry pick the men who would respond better. JMO.

[noahware in reply to gsun]

That's exactly what I first thought. Hey, wouldn't you want your trial to show really GREAT responses, almost universally? Why not eliminate guys who are least likely to respond?

But then I realized, there is no need to do that. Winning a game by 10 points is a "win" just as much as winning by 30 points. The med is already approved. What REALLY matters, strictly from a financial perspective, is NOT restricting the number of men who can be deemed eligible to receive your med. So it is not an issue that makes financial sense to be brought into play in the RCT.

I expect the suggestion for an FDG-PET will remain a hidden secret for some time, because ruling out a certain portion of otherwise eligible men, as unlikely to benefit from Pluvicto, would cut into Novartis revenues. Yes, this is cynical... but is it unrealistic?

[PHnerd in reply to noahware]

Thank you so much for this dialogue you two. I think I will consult with dad’s onc about doing the FDG scan. I’m not sure where you’re both located but I’m in Canada (Vancouver) and I can inquire if our provincial insurance might cover it.

[cesces]

While you go shop around for some second opinions and where you might get psma treatment, you should consider trying a few months of Bipolar Androgen Deprivation Therapy.

Lu177 is a serious treatment. There is a reason they limit the number of treatments you can get.

If BAT works for you you don't need to escalate. It definitely has some quality of life advantages over lu177. I understand it only works for about 25% or so of patients .

Though those numbers are old... they have learned a lot since then. Just with better screening their results are increasing.

Ask your treating doc what their current success rate is.

[Charles4212]

This thread has been very informative to me. I know think I was turned down for the Splash trial. Thanks