It tested whether giving Pluvicto increases radiographic progression-free survival (rPFS) in men who:
(1) have failed one of the second-line hormonals (abiraterone, enzalutamide, darolutamide, or apalutamide)
(2) have not had taxane chemo
(3) are metastatic and castration resistant (mCRPC)
(4) It was compared to following with one of the other hormonals. It does not show if it is better following with chemo.
The FDA may approve the new indication based on rPFS (i.e., they may not require full overall survival data, which would take years more). However, it isn't yet published, let alone submitted to the FDA, so it will be many months before approval. Meanwhile, patients can only get Pluvicto (or similar) by signing up for certain clinical trials:
I wish the control arm used docetaxel instead of the untried ARSi. (I'll use the abbreviation ARSi (androgen receptor signaling inhibitor) to mean abiraterone or enzalutamide (enza) or apalutamide or darolutamide)
Now we'll have to figure out best sequencing :
(1) Is ARSi -> Pluvicto -> docetaxel (as in the PSMAfore trial) better than ARSi/docetaxel>Pluvicto (as in the VISION trial)?
(2) Is ARSi -> Pluvicto -> docetaxel (as in the PSMAfore trial) better than enza>docetaxel+enza (as in the PRESIDE trial).
(3) The CARD trial said Jevtana (used after docetaxel) should come before the 2nd ARSi
(4) The TheraP trial said that after ARSi and docetaxel, Pluvicto should be used before Jevtana.
Lots of work has to be done before we know the best sequencing. Until then, we have to rely on judgment and shared decision-making.
The PSMAfore trial was only for men with mCRPC. Hopefully, the PSMAddition trial (primary completion in Aug. 2024) in newly diagnosed metastatic men will prove your results were not a fluke.
I feel the need to point out something about these Novartis Pluvicto trials (one of which I participated in). While you are given an initial PSMA-PET at screening (to confirm PSMA avidity), at no subsequent time was I given, or offered, further PSMA scans to help monitor progression.
How is "progression" confirmed, or not, as you proceed through the 36-week course of six infusions? Solely by way of bone scan and CT.
What do we know about CT and bone scans? That neither is particularly good at finding individual prostate cancer cells or very small tumors. A study showed PSMA scanning was far more accurate than the standard bone/CT approach at detecting metastases (92% versus 65%). So bone/CT has a WORSE ability to correctly identify when disease is present or progressing.
One paper (linked below) suggests that "the durability of responses for PSMA-based RNT [that is say, Pluvicto] is often short-lived, even in patients with initial responses. The mechanisms of how tumors develop resistance to PSMA-based RNT are currently not well understood [but] the therapeutic failure of 177Lu-PSMA appears to be linked in many cases to the progression of micrometastatic disease." ascopubs.org/doi/full/10.12...
The progression of micrometastatic disease, with tiny mets that can NOT be detected with a bone/CT scan? But that might possibly be detected with PSMA-PET? Hmmm.
If I had to do it all over again, I would have insisted on PSMA scanning at some point in the trial. As it now stands, I have no good idea what my disease is doing, except causing my PSA to go up month after month even as my MO claims we still don't know if that steady multi-month PSA rise means "progression" or not. All we know is that bone scans supposedly show "stable disease."
Thus, I am on record so far in this trial as a statistical "success" by meeting the primary endpoint of radiographic progresssion-free survival, as measured by less accurate/refined scans, even as I had a PSA progression (in rough terms) from 25 down to 2.5 and then up to 15 to 35 to 50 to 75, along with a significant rise in ALP.
Are they giving you SPECT scans? I sat in on a theranostics presentation from GE at the RSNA conference last week. It was heavy on prostate cancer and the new equipment they’re introducing for nuclear medicine. PET and SPECT were the bookends for the treatment regimen. Like you I don’t know how they would measure efficacy without follow up scans.
The trial protocol calls only for CT and bone scans, and that's how we went over the summer/fall. Nothing else. How I proceed from here is unclear, but I am posting primarily to inform men going into these trials that such scanning may not provide info that is as detailed as desired, so far as fully understanding efficacy. While that understanding may be YOUR goal, it is not the goal of the trial
I saw a Mayo presentation mentioning SPECT, very cool stuff. I am not allowed to post a link to it here, but you can find it on yt by searching "PSMA Scans & Pluvicto in 2022 -- Geoffrey Johnson."
Hey, a clinical trial offers free care... who can complain? But yeah, I would have preferred to be at Mayo for this.
SPECT can be used for Pluvicto treatment because it generates gamma rays in addition to beta particles. PET gives a stronger signal, so a separate PSMA PET indicator (like 68Ga-PSMA-11) is always used with it.
Imaging companies are betting big on treatments like Pluvicto becoming SOC in the very near future. I have to admit the new technologies are impressive. The new GE PET scanner is revolutionary according to their presentation.
"Participants must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained prior to randomization." and be CR by PSA and progressively metastatic as identified by soft-tissue progression or two new lesions on the bone scan. So only conventional imaging is used in this study to define radiographic progression.
PSMA-avidity is a separate eligibility criterion.
This seems appropriate to me for 2 reasons:
(1) Some of the progression may not be PSMA -avid
(2) Progression on a PSMA PET scan may occur earlier (for those who have PSMA-avid progression), but that is true for both the Pluvicto and the second ARSi control groups.
If the new indication is FDA-approved, patients will probably be monitored with PET scans.
Bone scans may be appropriate for use in the trial, but I am suggesting they may not be sufficient/satisfying for those patients who want to know every gory detail of what their cancer might be doing.
On the other hand, some men don't WANT all those details. Unless they are indisputably good, they tend to make you nervous.
But still I wonder: if as the linked paper suggests, the Lu177 "β-particles deliver high absorbed radiation to macrotumors but a lower absorbed dose to small metastatic cell clusters [meaning a] frequent progression pattern after treatment with 177Lu-PSMA is diffuse marrow infiltration [because] small-volume disease received an inadequate radiation dose," then wouldn't the treating doc have a much better chance of finding this small-volume disease with the more refined scans?
The bigger mets that are more easily knocked back are the ones most easily detected by bone scan. But if its true that Lu177 does a better job knocking off macrotumors than microtumors, then those bone scans COULD be telling an insufficient and misleading story for some men, who may have a rapidly growing number of microtumors that are going undetected..
A common thread with allot of trials, treatments, and getting clear data and evidence,. Does seem to be clear imaging, scans and finding solid consistent ways of clearly tracking imaging and testing of cancer?
Would you be able to have your MO schedule you for a PMSA scan now just to see if there is any spread? I think the rising PSA alone would warrant coverage by insurance.
I am a 85 year old male who was diagnosed with prostate cancer in 1999, and opted for radical surgery because the cancer had broken through the capsule. Five years later with the rise of the PSA, i had 33 radiation treatments which again dropped the PSA. Several years later with the rise of the PSA, we went to Hormone therapy with injection and pills. Chemo was next which i would never go through again......it didn't help. We did "Provenge", the cleansing of the blood , but again it didn't help that much. The cancer has started to metalize , and at this point we are starting Pluvicto tomorrow ( July 31, Monday. Haave NO idea of what to expect.......i was 61 when they found the cancer.
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Question about availability of Lu-177 therapy
How Long Does the FDA’s Real-Time Oncology Review Program Take to Approve New Drug Applications?
