PSMA-Targeted Therapy May Decrease PSA Levels in Metastatic Prostate Cancer Subset

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Patients with metastatic castration-resistant prostate cancer treated with radioligand therapy, a form of targeted therapy, had improvements in PSA levels and survival with favorable side effect profiles.

More than half of patients with metastatic castration-resistant prostate cancer treated with the radioligand therapy 177Lu-PSMA-I&T experienced decreases in prostate-specific antigen (PSA) levels of at least 30%, according to recent study findings.

Findings from this study were presented at the 2023 American Urological Association Annual Meeting in Chicago.

“PSMA-targeted radioligand therapy with lutetium PSMA-617 Is associated with prolonged overall survival in patients with metastatic castration-resistant prostate cancer, but data regarding the oncological efficacy and toxicity of lutetium PSMA-I&T are limited,” explained study author Dr. Derya Tilki, visiting faculty at Koç University in Istanbul, Turkey, and urologist at Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Germany.

For the study, a total of 33 patients with metastatic castration-resistant prostate cancer received a total of 88 cycles of 177Lu-PSMA-I&T.

Oncological outcomes measured included clinical progression-free survival, defined as the time from the first radioligand therapy cycle to any radiological or biological progression of the disease.

“We assessed response according to PSA changes and imaging response,” Tilki said.

The investigators also assessed side effects related to the treatment.

Median patient age at the time of first radioligand therapy cycle was 71.6 years. PSA response of any amount was seen in 22 patients (69%), at least 30% in 18 patients (56%), at least 50% in 11 patients (33%) and at least 90% in six patients (33%).

Clinical progression-free survival following the first cycle of radioligand therapy was 6.3 months, and overall survival following the first cycle was 21.4 months.

Regarding side effects, nephrotoxicity (what occurs when kidneys are damaged by a drug) was observed in four patients; this side effect was considered mild to moderate in two patients, moderate to severe in one patient and severe to life-threatening in one patient. Hematotoxicity (which can lead to bleeding, infection or anemia) was experienced by six patients (18.2%). The investigators also reported six patients with some degree of myelotoxicity (affecting the bone marrow).

Limitations of the study included its retrospective nature as well as the varying histories of the patients included in the study, according to Tilki.

“These are one of the few data for PSMA radioligand therapy with PSMA-I&T in contrast with PSMA-617, and the toxicity profile is very similar (to that of) PSMA-617,” Tilki said in her presentation of the data.

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