A recent phase 1/2 clinical trial has demonstrated encouraging results for ¹⁶¹Tb-PSMA-I&T, a novel radioligand therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). The study, known as the VIOLET trial, was conducted at the Peter MacCallum Cancer Centre in Melbourne, Australia, and aimed to evaluate the safety and efficacy of this innovative treatment.

Terbium-161 (¹⁶¹Tb) is a radionuclide that emits beta particles similar to the commonly used lutetium-177 (¹⁷⁷Lu) but also releases additional Auger electrons. These electrons have ultra-short path lengths, potentially enhancing the destruction of micrometastases and single cancer cells that may be less affected by beta radiation alone. Preclinical studies have indicated that ¹⁶¹Tb may offer superior efficacy compared to ¹⁷⁷Lu in targeting prostate cancer cells.

In the VIOLET trial, 30 men with progressive mCRPC, all of whom had previously received taxane chemotherapy and androgen receptor pathway inhibitors, were enrolled. Eligibility required PSMA-positive disease confirmed by PET/CT imaging. Participants received up to six cycles of ¹⁶¹Tb-PSMA-I&T intravenously every six weeks, with doses escalating through 4.4, 5.5, and 7.4 GBq to determine the maximum tolerated dose (MTD).

The treatment was well-tolerated, with no dose-limiting toxicities observed. The MTD was established at 7.4 GBq, and the safety profile was favorable, with few grade 3 or higher treatment-related adverse events reported. Notably, there were no treatment-related deaths.

Efficacy outcomes were promising: 70% of patients achieved a ≥50% reduction in prostate-specific antigen (PSA) levels (PSA50-RR), and 40% achieved a ≥90% reduction (PSA90-RR). The median PSA progression-free survival was 9.0 months, and the median radiographic progression-free survival was 11.1 months.

These findings suggest that ¹⁶¹Tb-PSMA-I&T could be a potent therapeutic option for patients with mCRPC, offering enhanced targeting of cancer cells with a manageable safety profile. Further studies, including a planned cohort to evaluate higher dosing, are warranted to confirm these results and potentially expand the use of ¹⁶¹Tb in prostate cancer treatment.

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