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PSMA radio tracers for scanning and treating main and metastatic Prostate Cancer

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Posted 23 Jan 2022 at 14:54

Perhaps this holds promise for the future.   'The dawning of the era of PSMA theranostics' or use of PSMA radio tracers to scan and treat main and metastatic Prostate Cancer.

Below is an article from 'PractiseUpdate' that I've adjusted trying to make it more layman friendly.  The original article is linked at the end.

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The dawning of the era of PSMA Theranostics

Some history of Prostate Cancer treatment

‘The decade between 2010 and 2020 saw more new therapies and imaging treatments for prostate cancer than were developed in the preceding 70 years.   From the initial demonstration of therapeutic orchiectomy by Higgins and Hodges in 1941 through 2010, new therapies were only approved once every several years.

Since the US approval of cabazitaxel and sipuleucel-T in 2010, we have seen more than one new drug approval per year for prostate cancer.   A list that includes abiraterone, enzalutamide, apalutamide, darolutamide, choline PET, radium 223, fluciclovine PET, rucaparib, and olaparib.    While this decade is notable in its own right, 2021 marks an inflection point in prostate cancer clinical care and research with the dawning of the era of PSMA theranostics.

 

PSMA background

PSMA is a cell-surface molecule that is selectively overexpressed on prostate cells and has limited expression elsewhere in the body. These characteristics make it attractive as a target for cell-specific PET imaging and as a potential target for therapeutics. The additional fact that PSMA is continuously circulated from the cell surface to the cytoplasm makes it additionally attractive as a vehicle to deliver therapeutics to prostate cancer cells.

 

PSMA Scanning

The US FDA has approved two PSMA PET imaging radiotracers, 18F-DCFPyL and 68Ga-PSMA-11.    Both are approved for the same indications — either as a staging exam in patients with suspected prostate cancer who are potentially curable by surgery or other therapy or for patients with biochemical recurrence after definitive local therapy.

 

PSMA treatment

The FDA has also granted priority review to 177Lu-PSMA-617 as a treatment for metastatic castration-resistant prostate cancer (mCRPC). This was based on the phase III VISION study1 as presented by Michael Morris at ASCO 2021.

The VISION study was a randomized study of 177Lu-PSMA-617 versus standard of care in men with mCRPC who had already received at least one androgen receptor pathway inhibitor (ARPI) and one or two taxane regimens. 

177Lu-PSMA-617 met the primary endpoint of an improved overall survival with an impressive hazard ratio for death of 0.62 (95% CI, 0.52–0.74). The safety profile was also favorable, with 23.5% of patients having grade 3 or greater myelosuppression, no patients having grade 3 or greater dry mouth, and fewer than 2% having grade 3 or greater nausea and vomiting. These data augment the previously presented phase II TheraP study2 from the ANZUP group, which showed the superiority of 177Lu-PSMA-617 over cabazitaxel in a post-ARPI, post-docetaxel setting.

 

Conclusions

The approval of the two PSMA-targeting imaging agents and the expected approval of 177Lu-PSMA-617 will change how prostate cancer is managed in the US.

The imaging studies will redefine disease states as clinicians will have to decide how to categorize patients who previously had no recognizable metastases but now have low-volume disease detectable only by PET. New treatment paradigms defining the role of adjuvant and salvage radiation therapy, local treatments for oligometastatic disease, and the border between non-mCRPC and mCRPC will have to be addressed.

The exact utilization of 177Lu-PSMA-617 will depend on the eventual FDA label, but trials to move 177Lu-PSMA-617 forward in the treatment algorithm and combine it with existing therapies are already underway. 

In many ways these approvals are only the beginning of a new era. Additional and completely different therapies targeting PSMA, such as bispecific antibodies and CART therapies, are already in trials. Separately and together, these approaches are expanding the diversity of the therapeutics options available for our patients. Clinicians and researchers will now be presented with perhaps more questions than answers as we integrate these new options, but it is a wonderful problem to have as the pace of progress in prostate cancer continues to accelerate.’

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Take a look at the orginal content on PracticeUpdate: http://prac.co/l/y69n3hzq

 

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Vision Trial info from Urotoday

The VISION trial is an international, randomized, open-label phase III study evaluating 177Lu-PSMA-617 in men with PSMA-positive mCRPC who had previously received treatment with next-generation androgen receptor signaling inhibition (abiraterone, enzalutamide, etc) and one or two prior lines of taxane chemotherapy. Additionally, patients must have had an ECOG performance status of 0-2 and a life expectancy of at least 6 months. Importantly, patients must have had PSMA-positive disease on the basis of a central review of 68Ga-PSMA-11 staging scans. PSMA positivity was defined as uptake greater in metastatic lesions than in the liver. Further, they could have no PSMA-negative metastatic lesions.

 

Regards
Peter

 
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