BARCELONA—High prostate-specific membrane antigen (PSMA) connected whole-body positron emanation tomography (PET) scans predicts a higher likelihood of favorable effect to lutetium-177 (177Lu)–PSMA-617 than to cabazitaxel successful patients with metastatic castration-resistant prostate cancer that has progressed aft docetaxel.
The researchers besides assessed a prognostic biomarker, fluorodeoxyglucose (FDG) PET. A precocious measurement of illness connected FDG-PET (metabolic tumor volume [MTV] > 200 mL) was associated with a worse prognosis careless of randomly assigned treatment, reported the pb researcher, James Buteau, MD, a atomic medicine doc from the Peter MacCallum Cancer Centre, Melbourne, Australia.
These are the latest results of the TheraP proceedings presented astatine European Association of Nuclear Medicine (EANM) 2022. The findings person implications for objective practice. "In this study, we amusement that PSMA-PET — a afloat assemblage scan — done anterior to attraction with 177Lu-PSMA-617, predicts however the attraction volition go," remarked Buteau, who presented the findings.
"It's a model into the future, truthful we tin peek done and spot however attraction volition spell for antithetic patients, due to the fact that the scans tin assistance america determine who should decidedly get attraction with 177Lu-PSMA-617, and who mightiness payment much from different treatments," helium added. "With FDG-PET, we besides place which patients volition bash worse and whitethorn payment much from different strategies, similar therapy combinations."
The findings whitethorn assistance clinicians determine which attraction to springiness first. "If you person a prime betwixt cabazitaxel oregon 177Lu-PSMA-617, past these biomarkers amusement which patients should decidedly spell connected to get the 177Lu-PSMA-617," said Buteau, whose abstract was awarded 1 of the apical 3 technological presentations astatine this year's meeting.
Therapy with 177Lu-PSMA-617 should beryllium prioritized for patients showing precocious PSMA concentrations, helium summarized, portion precocious FDG measurement warrants much probe for attraction intensification.
Which Patients Will Most Benefit From 177 Lu-PSMA-617?
The TheraP survey was the archetypal randomized controlled proceedings to comparison 177Lu-PSMA-617 with cabazitaxel successful men with metastatic castration-resistant prostate cancer. A full of 200 patients were randomly assigned 1:1 to 177Lu-PSMA-617 (8.5 GBq intravenously each 6 weeks, decreasing by 0.5 GBq each rhythm for up to 6 cycles) oregon to cabazitaxel (active chemotherapy astatine 20 mg/m3 intravenously each 3 weeks, up to 10 cycles).
Previously published findings amusement that 177Lu-PSMA-617 improved the prostate-specific antigen (PSA) ≥50% effect complaint (PSA50-RR), on with improved PSA progression-free endurance (PFS), and radiographic PFS compared with cabazitaxel successful this diligent group. It showed that 66% vs 37% of patients met PSA50-RR.
In the survey presented present today, Buteau analyzed the PSMA and FDG-PET scans obtained earlier medication of treatments to the 200 randomly assigned patients. "The survey efficaciously aimed to validate anterior biomarker work, targeting the apical 1 3rd of patients with these imaging parameters," said Buteau.
For the PSMA predictive biomarker, the PSA50-RR successful patients with a mean standardized uptake worth of 10 oregon greater was 91% with 177Lu-PSMA-617 vs 47% with cabazitaxel.
"What's singular is these are heavy PSA drops. Over 60% of them had an implicit 90% driblet successful PSA value. In examination to radical who had a mean SUV little than 10, for which 52% responded [with PSA 50] connected 177Lu-PSMA-617 successful vs 32% connected cabazitaxel," helium reported.
These results construe to an likelihood ratio (OR) of 2.2 successful patients with a mean SUV of little than 10 oregon little but an OR of 12.2 successful those with mean SUV of 10 oregon greater.
"So the higher PSMA intensity, past the amended the response," said Buteau.
When the FDG measurement was greater, the patients did worse: The PSA50-RR (all patients combined) was 38% erstwhile MTV was 200 mL oregon little vs 56% erstwhile MTV was little than 200 mL.
"So each successful all, FDG-PET helps to place men who mightiness bash amended from combinations oregon much intensive treatments, and mightiness beryllium seen arsenic a stepping chromatic successful guiding aboriginal trials alternatively than changing management," concluded Buteau.
Radiographic PFS shows that patients with little measurement bash a batch amended than those with higher measurement of FDG-avid disease, helium added.
Earlier this year, the U.S. Food and Drug Administration approved 177Lu-PSMA-617 for objective usage successful men with metastatic castration-resistant prostate cancer. "Now, for the galore atomic medicine centers that whitethorn privation to supply this treatment, this survey helps with enactment of patients who are astir apt to respond," explained Buteau. "It's astir assets allocation arsenic well."
Irene Burger, MD, atomic medicine doc signifier Kantonsspital Baden, Switzerland, commented connected the enactment for Medscape Medical News. "I deliberation this is important enactment due to the fact that it guides america successful optimizing diligent enactment for treatment. PSMA PET is bully to specify those with precocious look truthful we tin get capable radiation doses to the tumor, but we should besides see metabolic activity." She added, "With improved diligent selection, I'm convinced that we tin amended the efficacy of our caller drugs."
"These amusement that with reasonably precocious PSMA look with debased FDG uptake, you tin preselect patients that volition a greater than 95% accidental of bully response. To cognize this earlier you commencement attraction is tremendously adjuvant to springiness the due therapy for a patient."
Drs Buteau and Burger person nary applicable disclosures.
European Association of Nuclear Medicine (EANM) 2022. Presented October 16, 2022.
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