VISION Trial Results Being Released

[MateoBeach]

The results of the US Phase III Vision Trial of 177Lu-PSMA-617 for mCRPC are finally being released at the 2021 ASCO virtual assembly starting tomorrow. Here is a preview (spoiler alert they are positively positive!)

The international, randomized Phase 3 VISION trial, led by investigators Dr. Michael Morris (Memorial Sloan Kettering Cancer Center) and Dr. Oliver Sartor (Tulane University), enrolled more than 800 patients with mCRPC whose disease had progressed on other treatments. Patients also had to have a positive PSMA PET scan, meaning that their prostate cancer cells showed the PSMA protein on the surface. Patients were randomized to treatment with 177Lu-PSMA-617 + best standard of care vs. best standard of care alone.

The study results were positive. Patients treated with 177Lu-PSMA-617 were approximately 40% less likely to die and 60% less likely to have disease progression on scans vs. patients treated with standard of care alone. Median overall survival was 15.3 months for patients in the 177Lu-PSMA-617 arm vs. 11.3 months in the standard of care alone arm. Other measures in the trial also showed a significant benefit for 177Lu-PSMA-617.

In terms of side effects, some were more common among patients treated with 177Lu-PSMA-617 + standard of care vs. standard of care alone. These included fatigue (49.1% vs 29.3%), bone marrow suppression (47.4% vs 17.6%), dry mouth (39.3% vs 1%), and nausea/vomiting (39.3% vs 17.1%).

177Lu-PSMA-617 has not been approved by the FDA, though this trial data will be used as part of an application for FDA approval.

[MateoBeach]

This will be presented during the ASCO Plenary Session on Sunday June 6 between 10 AM and 1 PM.

[Tall_Allen]

I predicted 3-5 months, it came in at 4. It's like I have a crystal ball! 😎

[MateoBeach in reply to Tall_Allen]

Curious to see how many placebo patients dropped out.

[Tall_Allen in reply to MateoBeach]

7.8% of men treated with the best SOC arm discontinued SOC

[StayingOptimistic in reply to Tall_Allen]

Does 4 months mean a patient will live 4 months more than if he never used it? Or is this something for doctors to gauge the difference between using it or not using it? When someone says this is the median, I still don’t get it unfortunately. For example, can someone gets 4 years more if he uses it even though the media is 4 months? Thanks.

[Tall_Allen in reply to StayingOptimistic]

Yes, 4 months longer than the control group who got nothing but standard of care. Median means half did better and half did worse. There are often a few outliers who did especially well.

[Hidden in reply to Tall_Allen]

SOC = ADT?

[Tall_Allen in reply to Hidden]

SOC may be any of the medications and procedures approved for metastatic castration-resistant patients who has had at least one round of chemo infusions and has used either Zytiga or Xtandi.

[Hidden in reply to Tall_Allen]

Ty

[Danish-patient in reply to Hidden]

SOC is probably chemotherapy in this relation.

[monte1111 in reply to Hidden]

SOC + ADT = WTF

[Hidden in reply to monte1111]

That's the protocol I'm on. WTF Happened.

[Hidden in reply to Tall_Allen]

The bone marrow issue is little concerning to me...once the bone marrow goes nothing will be able to help. Or am I overstating this?

[Tall_Allen in reply to Hidden]

They have strict guidelines on pre-therapy bloodwork for that reason.

[lewicki in reply to Hidden]

Does the body regrow the bone marrow loss? What supplements might help this?

[Hidden in reply to lewicki]

You are asking the wrong person. Try TA.

[lewicki in reply to Hidden]

Ok Thanks

[GoBucks]

47% bone marrow suppression. I know the results sound good but that sounds bad.

[Spyder54]

Great News! Where we all hoped LU-177 was heading. Thank you Mateo Beach.

[Hidden]

At the risk of sounding crass, is the additional 4 months really considered a big deal in the medical world?

[Hidden in reply to Hidden]

Probably not in the medical world but definitely in the patient world.

[StePeteMN in reply to Hidden]

I think we look at that 4 months in the context of patients who had very advanced disease. At risk of sounding morbid, It seems, statistically, that a trial works best with patients who are at risk of being near end of life. I remember this light bulb turning on over my head as an oncologist explained to me the benefit of taxotere chemo using the Stampede trial as an example. In that trial, patients who had the docetaxel lived 10 months longer than men who had standard treatment alone! ... I have lived already way longer than 10 months since chemo!!

[MateoBeach in reply to StePeteMN]

👍

[Tall_Allen in reply to Hidden]

Yes.

[Danish-patient]

Very timely report in my personal perspective - I have just entered Austria to have my 11th (!) PSMA Lutetium treatment here in Innsbruck at the University Hospital.

[lewicki in reply to Danish-patient]

What is the dosage?

[Danish-patient in reply to lewicki]

My last treatment - cycle 10 - was 7.756 GBq.

[lewicki in reply to Danish-patient]

My dosage was 4GBQ LU-177 and AC-225. Not sure why thy did it that way. Do they do AC-225 in Austria?

[Danish-patient in reply to lewicki]

You have received the so-called tandem treatment, where PSMA is used with partly lutetium and partly actinium. The latter delivers alpha radiation, which delivers more energy than the beta radiation from lutetium.They don’t do this tandem treatment in Austria because of more intense side effects. It has been used in Bad Berka in Germany.

[lewicki in reply to Danish-patient]

I had dry mouth and still do but getting much better. As a result of these treatments I had 6 crowns with root canals fall out . To much bacteria from dry mouth and the radiation I suspect. For some reason the doctors at University of Heidelberg gave me this combination. May be they thought just LU-177 was not good enough or I was research. Not a problem. Loss of teeth and dry mouth a fair trade off to get PSA > 0.1.I have been off ADT since October. I have been to Austria in 2013 when I visited nSt Georg Klinik in Bad Abling for Transurthral Hyperthermia for my cancr . Beautiful part of the world.

[Danish-patient in reply to lewicki]

Dry mouth can cause problems beyond the irritation of having it. Why are you off ADT? Seems to be a chance to take?

[lewicki in reply to Danish-patient]

Two doctors an oncologist and urologist suggested it. I was diagnosed June 1999. I am now 80. T is 5. Need a break. Take a vacation. Just wanted to feel good again.

[dhccpa]

Adds four months?

[Shooter1 in reply to dhccpa]

Yep, that's all. How long is the treatment to get that 4 mo???

[dhccpa in reply to Shooter1]

It would be nice if they told more detail about the longest times that people survive under each scenario--not just the median. And of course more details on those long term survivors.

[6357axbz in reply to dhccpa]

Ha, I was just about to ask the same question. We have the median but what was the range?

[Tall_Allen in reply to 6357axbz]

They can't run trials forever, if you want answers in a reasonable time frame. It looks like about 30% were still alive after 2 years, if that helps.

[6357axbz in reply to Tall_Allen]

So the lead spokesman states, “The next step, Kishan said, would be to look at whether the drug might be even more effective in patients with earlier stage cancers. “But that should be done in a clinical trial,” he added.

Based on the way this drug has been shown to work why would yet another CT be required for hormone naive mPCa?

[Tall_Allen in reply to 6357axbz]

Only if you want Medicare/insurance to cover it for earlier use. And we also know its effectiveness and lack of toxicity depends on sufficient PSMA avidity. PSMA is not well-expressed very early.

[6357axbz in reply to Tall_Allen]

It seems to be expressed pretty well with me and other mHSPCa patients here. How do you define “well expressed”?

[Tall_Allen in reply to 6357axbz]

SUVmax well over background.

[MateoBeach in reply to Tall_Allen]

I had a repeat PyL PSMA scan at the LA VA health center on Friday. 18 mo post PLN RT. Their new more sensitive scanner lit up a newly seen retro peritoneal node at aortic bifurcation. Will have my RO see how it aligns with the prior treatment field. Anyway, in discussing with Dr. Gholam Berenji there he said VISION required 10X SUVmax. (Guess that refers to vs. blood pool). But that for selecting patients for treatment probably SUVmax of >5 would be reasonable.

[Tall_Allen in reply to MateoBeach]

There is some controversy in how to define "avid." As you said, VISION defined it in relation to background, but the Australians use an absolute SUVmax. There is also controversy between the 2 groups on the concurrent use of FDG.

[Savoy]

I should know this answer, but...is it possible to tell how long it might be before this goes into standard practice?

[Tall_Allen in reply to Savoy]

After FDA approval.

[EdBar]

I’m interested in hearing the details of the outcome. During my recent 6 month visit with Dr. Sartor recently he was very upbeat about the results, of course he couldn’t give me details prior to his presentation. Perhaps there was a subgroup that did exceptionally well like there was with Provenge, we’ll see.

Ed

[Cooolone]

Always see the end points of these ... But other than being PSMA sensitive, what are the entry points? What difference between different patient stratification? Metastatic disease comes in all shapes and sizes so it's all interesting, but I'll like to see the data.

[dhccpa in reply to Cooolone]

Amen

[Tall_Allen in reply to Cooolone]

At least one chemo and at least one advanced hormonal. Other minimal bloodwork had to be OK. PSMA avid on PET scan.

[MateoBeach in reply to Cooolone]

There is much more data from outside the USA published such as from Germany and Australia etc where they have more experience and have/are running varied trials.

[HopingForTheBest1]

225Ac-J591 may be an even better option. Tagawa at Weill Cornell is researching this.

[lewicki in reply to HopingForTheBest1]

My treatment at the university of Heidelberg of Lu-177 and AC-225 PSA is less than 0.1. Last infusion was July 2020.

[Jackpine in reply to lewicki]

I will be able to use LU again when approved. Not sure if there is a limit longer term.

[JPnSD]

So the real hope is that this might have much better results for patients that receive it earlier than those on the trial? I heard the word "cure" used in one of the news reports on this when used on patients much earlier in their journey. Any basis?

[Danish-patient in reply to JPnSD]

PSMA lutetium has equally good results an early stage in the disease for those sensible to PSMA. But it is not a cure for aggressive PCa. However, it can make PCa an almost chronic disease that you can live with.

[Tall_Allen in reply to JPnSD]

None.

[kiskadog in reply to JPnSD]

My experience; I was diagnosed at UCSF November 2018. I was treated early on at Bad Berka, by Dr Baum and his associates, in May, 2019. I had multiple lymph nodes that lit up plus one bone met on a rib. They administered a single dose of Lu177, and asked me to monitor my PSA monthly, and contact them if it rose.I stayed on lupron injections, and aberaterone acetate for about a year, while my PSA dropped to undetectable(<0.02).

I had severe sleep disruption and deprivation due to the ADT, and though my Oncologist refused to help me, in any way decide, I decided to quit the ADT.

Now just over one year later my PSA remains undetectable, and I get a little better sleep. Instead of hot flashes every 45 minutes to an hour, they come on 1-1/2 to 2 hours at night.

My QOL is greatly improved, and though nearing 72, I continue working (self employed building maintenance, operate a B&B, and well drilling).

Without any help from my oncologist, I am flying blind. I am trying to decide what if anything to do next. I live in rural Alaska, so local medical help is quite limited.

I feel quite lucky at this point, but would entertain any suggestions.

[Jackpine]

I was part of the trial and has good results. PSA went from 110 to 0.4 in four infusions. That was 2.5 years ago so don’t sweat the 4 months. I’ve have other treatments since the but doing well

[lewicki in reply to Jackpine]

Can you do LU-177 again when it is available?

[Tall_Allen in reply to Jackpine]

4 months is the survival increase.

[Jackpine in reply to Tall_Allen]

I understood the 4 month survival. My point is it can be much longer especially with further treatments. I like LU177 as side effects were minimal and it’s and effective treatment for some.

[Tall_Allen in reply to Jackpine]

No. Having looked at the KM survival curve, it looks like the 4 month advantage seemed to hold no matter how long they survived.

Side effects were not minimal -- serious drug-related treatment emergent adverse events (TEAEs) occurred in 28% of men taking 177Lu-PSMA-617 vs 4% of men taking best SOC. Most of the serious TEAEs that were worse were blood related - red blood cells, white blood cells and platelets. Others included fatigue, UTIs, blood in urine, hypertension and kidney injury.

[Hidden]

Can you have this after Radium 223?

[Tall_Allen in reply to Hidden]

It wasn't allowed in the trial, so it won't be approved.

[Hidden in reply to Tall_Allen]

Thanks. My husband has had Zytiga, and Taxotere and PSA going up. They want to start him on Radium 223. Don't know if we should do that or wait for the LU 177. PSA is going up slowly, but still going up.

[Tall_Allen in reply to Hidden]

Or get on the Th227 trial, which will, in effect, give you both.