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SAN FRANCISCO -- A novel, targeted radionuclide therapy showed promising activity and overall survival for heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) patients, the phase II found.

At a median follow-up of nearly 2 years, overall survival was 13.3 months (95% CI 10.5-18.0) among 50 patients with prostate-specific membrane antigen (PSMA)-positive mCRPC treated with lutetium-177 PSMA-617 (¹⁷⁷Lu-PSMA-617), reported Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne, Australia.

"While my strong impression is that this is a life-prolonging therapy, this is not a claim that we can make yet, because there's no comparator arm," Hofman said during a press briefing ahead of the Genitourinary Cancer Symposium here.

High response rates and low toxicity were seen with the treatment, and he noted that the survival data in the single-arm study compared favorably to historical averages of 9 months for this group of patients.

In prostate tumors, PSMA expression is 100 to 1,000 greater than in normal tissue, with expression further increased in patients with mCRPC. PSMA-617 is a small molecule that binds to PSMA, and with ¹⁷⁷Lu attached, delivers beta-radiation directly to tumor cells.

In the LuPSMA trial, the investigators "personalized" the therapy by conducting a PET scan in each participant prior to treatment to ensure their disease sufficiently expressed PSMA and would therefore be more likely to respond to ¹⁷⁷Lu-PSMA-617.

In all, 74% of patients had a prostate-specific antigen (PSA) decline of ≥30%, 64% had a PSA decline of ≥50%, and 44% had a PSA decline of ≥80%. Median overall survival was 18.0 months for the 37 patients with a PSA decline ≥50% compared with 8.7 months for those with a decline of <50% (P=0.001).

"There's only two patients that had no reduction in PSA, and we think this is probably a feature of our careful selection of patients with the PET scanning upfront to really enrich the study for patients that were likely to benefit from the treatment," Hofman said, explaining that from 20% to 30% of all mCRPC patients overexpress PSMA to a level that would make them eligible for the treatment.

The results of the trial have led to two phase III trials, one of which is while the other -- the -- is testing the agent against best standard of care.

"This is a very intriguing agent, and the VISION study is open in the U.S., which is a registration trial," said briefing moderator Robert Dreicer, MD, of the University of Virginia in Charlottesville and an American Society of Clinical Oncology (ASCO)-designated expert.

The current study enrolled 50 men, with a median age of 71, excluding 16 patients because of insufficient PSMA uptake on their PET scan. Prior therapies included abiraterone (Zytiga), enzalutamide (Xtandi), or both in 90%; docetaxel in 84%; and cabazitaxel in 48%.

"All men really had quite aggressive disease as evidenced by the PSA doubling time," said Hofman, noting that PSA levels were doubling on average every 2.6 months.

Patients received a median of 4 treatment cycles, with eight patients stopping earlier than that due to "exceptional response" and 10 patients due to disease progression. Retreatment with ¹⁷⁷Lu-PSMA-617 seemed feasible. In 14 patients who had initially responded but later progressed, treatment was re-administered; nine of these patients responded again with a PSA decline of ≥50%. For this group of 14 patients, median overall survival was 33 months.

An from Hofman's group, of 30 patients treated with ¹⁷⁷Lu-PSMA-617, found that the most common adverse events associated with the treatment were grade 1 dry mouth in 87%, and grade 1/2 transient nausea and fatigue in 50% each. Grade 3/4 thrombocytopenia that was considered to be possibly due to the study drug occurred in 13% of patients.

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