The FDA has only approved one kind of PSMA PET indicator (Ga68PSMA11) to qualify for Pluvicto. Two kinds of PSMA PET indicators are FDA-approved for recurrent patients and high-risk patients: Pylarify and Ga68PSMA11.
Pylarify, made by Progenics pharmaceuticals, is widely available:
Ga68PSMA11 was originally only approved at UCLA and UCSF for recurrence/high-risk. In December 2021, Telix pharmaceuticals also obtained FDA approval for those indications only and call it Illucix. They announced it will be available at 140 nuclear pharmacies across the US:
Now, the FDA has approved Ga68PSMA11 for the new indication - to determine eligibility for Pluvicto. But they did NOT approve Pylarify for the new indication. In the approved prescribing information, they wrote "Select patients for treatment using LOCAMETZ® or an approved PSMA-11 imaging agent based on PSMA expression in tumors."
Both Pluvicto and Locametz are manufactured by Novartis and will probably get distributed together, so it shouldn't be too big of a problem. What this means for patients, is that those who may already have the Pylarify PET scan will be unable to use it to qualify for Pluvicto. They will have to get a new PET scan. It's too bad because Pylarify is a more sensitive PET indicator. Plus, there are several new PSMA PET indicators in clinical trials - they will all require separate FDA approval. Medicare and insurance usually comply with FDA-approved indications.
I believe, along with researchers at Peter Mac in Australia, that it is prudent to also obtain an FDG PET scan before Pluvicto. FDG is important (not Axumin, C-11Choline or NaF(18)) because discordance is most likely to occur as metastases mature. However, I understand the argument that survival improvement occurred for most patients even without FDG:
Here in this question about the need for visualization using 18F-FDG - I will support you, Allen, with both hands! Although I have not heard of randomized trials on this score...)) I also try to convince all patients who come to me that it is necessary to undergo a PET-CT examination with FDG in order to assess the expected therapeutic efficacy of the upcoming treatment with the PSMA ligand.. But, to my regret, even many oncologists believe that imaging with FDG for prostate cancer does not provide any information..(( Meanwhile, the presence of more than 50% FDG(+) cells in the tumor negates the therapeutic effectiveness of treatment with PSMA! The picture shows the results of an FDG scan of a now deceased patient with prostate cancer.. He was immediately denied treatment with 177Lu+225AC - PSMA, but the patient insisted and decided to try to be treated for his money.. He underwent two courses of therapy, but, alas, to no avail, his PSA began to grow even faster.. The effect of substitution of malignant cells from PSMA(+) to FDG(+) occurred very quickly:
R.S. For those who do not know: Visualization with FDG is very easy to distinguish from other types of PET-CT examinations by the large physiological accumulation of FDG in the brain!
PET-CT imaging using RFP 18F-FDG of a patient with prostate cancer.
For comparison, visualization with 18F- FDG of a patient with prostate cancer who has a negative status to this rfp. The scan was performed on the same PET-CT equipment! This patient has successfully completed four courses of therapy 177Lu+225Ac - PSMA-617 with excellent results!
The patient's status is negative! Black is the place of physiological accumulation of FDG.
Thanks Allen, so I googled Pluvicto. This is LU-177, and FDA approved this week? I read the stats between Pluvicto, Jevtana, and Xofigo. They all seem to extend about 12-14 months overall survival for hormone resistant, metastatic PCa. With Pluvicto not working great for about 33% of men. Timing seems key to not be early or late for fear of strengthening non PSMA avid PCa cells. Do I have that right?
Timing still has to be worked out, but I suspect you are right. There is a sweet spot when PSMA is maximally expressed on metastases, but before mutations have occurred where too many cells have changed from fat metabolism (where they would show up on a C-11 Choline PET scan) and protein metabolism ( where they would show up on an Axumin PET scan) to sugar metabolism (where they show up on an FDG PET scan). I'm concerned about treating the PSMA-avid cells when there are too many non-PSMA-avid cells. It only gives the non-PSMA-avid cells more room and nutrients to grow. It might make the cancer progress more quickly. And if there aren't enough PSMA-avid cells, the radioactive "therapy" may only cause toxicity in the bone marrow, liver, and kidneys, not to mention the salivary glands and tear ducts.
Combination could be tested with Docetaxel too which is what my onco is trying for early HS PSMA avid bone mets plus something going on in prostate probably.
HT/ Lu-17 x 3 onto chemo x 3
Haven’t seen this suggested as a trial anywhere but I said yes!
Let us know if he starts that trial. There is a trial of Pluvicto combined with a PARP inhibitor. Based on the encouraging results of PARPi+abi in men who are not BRCA+, it sounds like a good combo. The PARPi finishes off the calls that are sublethally killed by Pluvicto.
Yes, Probably. The current big trial is for patients who are newly diagnosed with PSMA-avid metastases. Advanced hormone therapy temporarily increases PSMA-avidity. I'm not sure about using RT with it - that may only increase toxicity - but maybe if some metastases are very large or are not PSMA-avid.
Switzerland (and probably other places in Europe) offers 18F-PSMA PET-CT and PET-MRI. A cursory look at the publications indicate that 18F-PSMA is comparable to Pylarify (some differences as to where it accumulates in different organs due to metabolism) - is there any talk of approval of this in the U.S.? usz.ch/en/clinic/nuclear-me...? It seems they moved away from 68Ga-PSMA, probably due to easier production of the 18F-PSMA marker.
Also offered is 68Ga-dotatate for finding neuro-endocrine tumors - is this ever used in advance PCa?
While prudent to obtain an FDG PET scan before Pluvicto, I assume this would probably not be covered by Medicare and/or most insurers (as "medically unnecessary")? And so this would be paid out of pocket by most men, if they wanted to pursue?
I was considering doing so, as I was just randomized into the Lu177 arm of the Novartis chemo-naive trial, but I also just discovered that results of my recent PSMA PET that qualified me for the trial are currently unavailable to me. So I guess I will just take my chances, and be thankful for that opportunity.
When I mentioned getting the FDG scan as well I was told that comparison to the Pylarify scan is still being studied. Not the exact wording but a general blow off of my inquiry.
The Australian position about this is not widely accepted in the US. I pressed for it for a patient. Unfortunately, he had the "discordant" type, so an international team of nuclear medicine specialists in the US, Germany and Australia recommended against Lu177PSMA for him.
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Screening for Pluvicto
PSMA PET scan
Accuracy of PSMA PET scan?
Why the need for an FDG scan in addition to a PSMA scan?
Recent PSMA (Pylarify) PET Scan…. Covered by Medicare.
