Radioligand Therapy With [177Lu]Lu-PSMA I&T Shows Promising Safety, Efficacy in Elderly Patients With Prostate Cancer

A recent study presented at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting by Simon Weber, of the Clinic and Polyclinic for Nuclear Medicine at Würzburg University Hospital in Germany, assessed the safety and efficacy of [¹⁷⁷Lu]Lu-PSMA I&T radioligand therapy (RLT) in elderly patients with metastatic castration-resistant prostate cancer (mCRPC). This trial, focusing on men aged 75 years and older, explored how well these patients tolerated the treatment and identified key prognostic factors for overall survival (OS).

Prostate cancer predominantly affects older men, with the highest incidence observed in individuals over 75 years old. Given this demographic’s vulnerability, evaluating the safety and effectiveness of novel therapies like prostate-specific membrane antigen (PSMA)-targeted RLT using [¹⁷⁷Lu]Lu-PSMA I&T is crucial.

The study involved 56 men aged 75 years or older diagnosed with mCRPC. The participants received [¹⁷⁷Lu]Lu-PSMA I&T, and researchers monitored adverse events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. They also recorded baseline liver function, lactate dehydrogenase (LDH), C-reactive protein (CRP), and Gleason scores. Prostate-specific antigen (PSA) levels were measured after each RLT cycle, and metastatic spread was assessed in various body regions. The study used univariable and multivariable Cox regression and Kaplan-Meier analyses to identify factors associated with OS.

The median age of participants was 78 years, and they received a median cumulative activity of 18.2 GBq [¹⁷⁷Lu]Lu-PSMA I&T over a median of 3 cycles. The study found no grade 3 or higher AEs. Mild hematologic AEs, including anemia (21%), leukocytopenia (17%), and thrombocytopenia (7%), made up the observed grade 1/2 AEs. Renal function showed a minor decline, with grade 1/2 AEs related to estimated glomerular filtration rate observed in 19% of patients.

The median OS was 11 months, with 60.7% (34/56) of patients dying during the study period. Notably, 80.9% of patients experienced a PSA reduction following therapy, with 23 out of 38 achieving more than a 50.0% decrease. Univariable analysis revealed that lower baseline levels of PSA, CRP, LDH, aspartate aminotransferase, alkaline phosphatase, and hemoglobin were significantly associated with longer OS. Multivariable analysis confirmed that baseline PSA and LDH were significant predictors of OS, while PSMA positive tumor volume and CRP were not.

Patients exhibiting a PSA response after RLT had a significantly longer median OS of 21 months compared with 7 months for those without a PSA response. The combination of Response Evaluation Criteria In PSMA PET/CT (RECIP) and Prostate Cancer Working Group Criteria 3 (PCWG3) measures for assessing response highlighted a significantly shorter OS for patients with progressive disease (11 vs 22 months).

The study authors conclude that [¹⁷⁷Lu]Lu-PSMA I&T RLT is safe for patients aged 75 years and older, with outcomes comparable with those observed in younger patients. Lower baseline PSA and LDH levels were associated with longer OS, underscoring the prognostic value of these markers. A biochemical response to RLT, indicated by a decrease in PSA levels, significantly predicted longer survival. The findings suggest that combining RECIP and PCWG3 criteria provides a more comprehensive assessment of treatment response.