High PSMA predicts targeted therapy response in prostate cancer

Barcelona—High prostate-specific membrane antigen (PSMA) on whole-body positron emission tomography (PET) scan predicts a likely favorable response to lutetium-177 (177Lu)–PSMA-617 is superior to cabazitaxel in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel.

The researchers also evaluated a prognostic biomarker, fluorodeoxyglucose (FDG) PET. Massive disease (metabolic tumor volume) on FDG-PET [MTV] > 200 mL) was associated with worse prognosis, regardless of randomly assigned treatment, said principal investigator James Buteau, a nuclear medicine physician at the Peter MacCallum Cancer Center in Melbourne, Australia. the doctor reported.

These are the latest results from the TheraP trial presented at the European Society for Nuclear Medicine (EANM) 2022. This result has implications for clinical practice. “This study shows that PSMA-PET — a full-body scan — was done before treatment. 177Lu-PSMA-617 predicts how treatment will proceed,” said Buteau, who presented the findings.

“This is a window into the future, where we can get a peek at how treatment for different patients progresses, because scans can help us decide who should definitely get treatment. 177Lu-PSMA-617, and who may benefit more from other therapies,” he added. We can also identify which other strategies might be more profitable.”

The findings may help clinicians make initial treatment decisions. “If you have a choice between cabazitaxel or cabazitaxel 177For Lu-PSMA-617, these biomarkers indicate which patients should definitely receive treatment. 177Lu-PSMA-617.

treatment with 177Lu-PSMA-617 should be prioritized for patients with high PSMA concentrations, he summarized, but high FDG dose warrants more research for treatment intensification.

Which Patients Benefit Most 177 Lu-PSMA-617?

The TheraP study was the first randomized controlled trial to compare. 177Lu-PSMA-617 with cabazitaxel in men with metastatic castration-resistant prostate cancer. A total of 200 patients were randomly assigned 1:1. 177Lu-PSMA-617 (8.5 GBq intravenously every 6 weeks, decreasing by 0.5 GBq each cycle up to 6 cycles) or cabazitaxel (aggressive chemotherapy at 20 mg/m)3 up to 10 cycles every 3 weeks).

Previously published findings were 177Lu-PSMA-617 improved PSA progression-free survival (PFS) and radiographic PFS compared to cabazitaxel in this patient group, together with prostate-specific antigen (PSA) ≥50% response rate (PSA50 -RR) has been improved. It was shown that 66% vs. 37% of patients met the PSA50-RR.

In a study published here today, Buteau analyzed PSMA and FDG-PET scans obtained before treatment in 200 randomly assigned patients. “This study aimed to effectively validate previous biomarker studies in the top third of patients with these imaging parameters,” he said. .

For the PSMA predictive biomarker, PSA50-RR was 91% for patients with mean standardized uptake values ​​≥10. 177Lu-PSMA-617 vs cabazitaxel 47%.

“It is worth noting that these were severe PSA declines. More than 60% of people had PSA values ​​that were more than 90% lower. I answered. [with PSA 50] upon 17732% of Lu-PSMA-617 versus cabazitaxel,” he reported.

These results give an odds ratio (OR) of 2.2 for patients with a mean SUV of 10 or less, compared to an odds ratio (OR) of 12.2 for those with a mean SUV of 10 or more.

“So the higher the PSMA intensity, the better the response,” says Buteau.

The higher the FDG dose, the worse the patient. For MTV <200 mL, the PSA50-RR (for all patients combined) was 38%, whereas for MTV <200 mL he was 56%.

“Overall, FDG-PET will help identify men who may benefit more from combination therapy or more intensive therapy, rather than change management, to guide future trials.” It could be seen as a stepping stone for,” Buteau concluded.

Radiographic PFS shows that patients with low-load FDG-rich disease are much better than those with high-load disease, he added.

Earlier this year, the U.S. Food and Drug Administration approved 177Lu-PSMA-617 is for clinical use in men with metastatic castration-resistant prostate cancer. “For the many nuclear medicine centers that now want to offer this treatment, this study will help them select patients who are most likely to respond,” he explained Buteau. The same is true for resource allocation.”

Irene Burger, MD, MD, Doctor of Nuclear Medicine, Kantonsspital Baden, Switzerland Medscape Medical News“I think this is an important task because it guides us in optimizing patient selection for treatment. Adequate radiation doses can be obtained, but metabolic activity must also be considered.”

“These indicate that patients with low FDG uptake and moderately high PSMA expression can be preselected with a greater than 95% chance of a favorable response. Knowing is very helpful in giving the right treatment to the patient.”

Dr. Buto and Dr. Berger have no relevant disclosures.

European Society of Nuclear Medicine (EANM) 2022. Presented on 16 October 2022.

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