Full Article Title:
High PSMA Predictive of Good Response to Radioisotope Therapy in Prostate Cancer — But expert says trial findings might be more meaningful with OS focus (see commentary below)
MedPage's Mike Bassett provides his usual succinct overview of the Phase II findings in recent Australian trial (TheraP) using PSMA treatment vs cabazitaxel:
High baseline prostate-specific membrane antigen (PSMA) uptake on PET was predictive of a favorable response to treatment with lutetium-177 PSMA-617 versus cabazitaxel (Jevtana) in men with previously treated castration-resistant prostate cancer, reported Michael S. Hofman, MBBS, of MacCallum Cancer Centre in Melbourne, Australia, and colleagues.
The intial phase of TheraP "showed that treatment with lutetium-177 [177Lu]Lu-PSMA-617 improved frequency of prostate-specific antigen (PSA) response rate and progression-free survival compared with cabazitaxel in men with metastatic castration-resistant prostate cancer."1
This second phase "aimed to analyse gallium-68 [68Ga]Ga-PSMA-11 PET (PSMA-PET) and 2-[18F]fluoro-2-deoxy-D-glucose PET (FDG-PET) imaging parameters as predictive and prognostic biomarkers in this patient population."1
1. From the Background Summary in the referenced LANCET paper.
Bassett goes on to say that:
Among patients with a baseline PSMA-PET mean standardized uptake value (SUVmean) ≥10, 91% (n=32/35) treated with lutetium-177 PSMA-617 had a PSA response (defined as a decline in PSA of ≥50%), compared with 47% (n-14/30) treated with cabazitaxel (odds ratio 12.19, 95% CI 3.42-58.76 vs 2.22, 95% CI 1.11-4.51, adjusted P=0.039), they stated in the Lancet Oncology.
Additionally, high FDG-PET molecular tumor volume (MTV) was associated with lower responses, regardless of the assigned treatment, the authors noted.
"[177Lu]Lu-PSMA-617 should be prioritized in men with metastatic castration-resistant prostate cancer with high PSMA-PET SUVmean, while FDG-PET MTV can identify men with worse prognosis, warranting further research for treatment intensification," they said.
Significant findings include:
In the current analysis, Hofman's group assessed PSMA-PET and FDG-PET as predictive and prognostic biomarkers for this patient population.
An SUVmean of 10 or higher on PSMA-PET was evaluated as a predictive biomarker for response to lutetium-177 PSMA-617 versus cabazitaxel. An MTV of 200 mL or higher on FDG-PET was tested as a prognostic biomarker.
At a median follow-up of 18.4 months, high uptake on PSMA-PET was reported in 35% (n=35/99) of men who were assigned to the radionuclide group and 30% (n=30/101) of men in the cabazitaxel group. High-volume disease on FDG-PET (MTV ≥200 mL) was reported in 30% (n=30/99) and 30% (n=30/101), respectively.
Hofman and colleagues found that even among men with a low uptake (PSMA-PET SUVmean of less than 10), PSA responses were more frequent in those who were assigned to lutetium-177 PSMA-6176 (52% vs 32% in the cabazitaxel group).
They also reported that lower PSA response rates were seen in men with FDG-PET MTV of 200 mL or higher (38%) than in men with FDG-PET MTV less than 200 mL (56%). After adjusting for randomized treatment, the odds of PSA responses were significantly lower in patients who had FDG-PET MTV of 200 mL or higher versus patients who had FDG-PET MTV of less than 200 mL (OR 0.44, 95% CI 0.23-0.84, adjusted P=0.035).
There seems to be some criticism of the trial coming from VISON trial lead researcher, Dr. Oliver Sartor. A bit of international research "sticks and stones"? As patients, all information from these trials gives us a better framework to make critical decisions about treatment options. The Aussies and Germans have lead the way in PSMA diagnostics and therapeutics. A little bit of humble gratitude might well be in order from researchers here in the US - as in on the shoulders of . . . PSMA Theranostics hold the promise of being curative for some subset of PCa patients. I view that as real progress for a disease that, once metastatic, currently has no cures.
Here is the MedPage Today article:
High PSMA Predictive of Good Response to Radioisotope Therapy in Prostate Cancer - But expert says trial findings might be more meaningful with OS focus, by Mike Bassett, Staff Writer, MedPage Today, October 17, 2022
medpagetoday.com/radiology/...
And a link to the full The Lancet paper:
PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial, THE LANCET Oncology, Published:October 16, 2022
thelancet.com/journals/lano...
The Sartor comment is behind a paywall, but here is the link to it for those who might have access:
Predicting benefit from [177Lu]Lu-PSMA-617 therapy: what do we need to know?
thelancet.com/journals/lano...
And the ANZUP 1603 - ASCO paper mentioned in th article:
TheraP: 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel—Overall survival after median follow-up of 3 years (ANZUP 1603) - Meeting Abstract | 2022 ASCO Annual Meeting
ascopubs.org/doi/abs/10.120...
And here is the link to last year's paper on Sartor's VISION trial:
Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer - N Engl J Med 2021; 385:1091-1103 - September 16, 2021
nejm.org/doi/full/10.1056/n...
We now have larger patient populations using PSMA for both diagnostic and theranostic purposes. As a HS metastatic patient, I am hopeful that PSMA lives up to its potential and eventually becomes available to HS patients outside of the current CT-only setting here in the US.
Be Safe & Well,
Paz - K9
Androgen Receptor Activity (ARA) for BAT
