Safety and Survival Outcomes of¹⁷⁷Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer with Prior²²³Ra treatment: The RALU Study

Abstract

The RAdium LUtetium (RALU) study evaluated the feasibility of sequential alpha and beta emitter use in patients with bone-predominant metastatic castration-resistant prostate cancer.Methods: This pre-planned, interim, retrospective analysis investigated safety and survival outcomes with lutetium-177-PSMA ( 177 Lu-PSMA) in patients treated with prior radium-223 ( 223 Ra). Results: Forty-nine patients were evaluated. Patients received a median of 6 223 Ra injections; 59% of patients received 4 177 Lu-PSMA cycles. Most (69%) patients received 4 lifeprolonging therapies before 177 Lu-PSMA. Common Terminology Criteria for Adverse Events Grade 3−4 treatment-emergent adverse events during 177 Lu-PSMA therapy and a 30-day followup period included anemia (18%) and thrombocytopenia (2%). Median overall survival was 12.6 (95% CI 8.8-16.1) and 31.4 months (95% CI 25.7-37.6) from starting 177 Lu-PSMA or 223 Ra, respectively. Conclusions: 177 Lu-PSMA treatment was well tolerated in patients who had received prior 223 Ra. 223 Ra use before 177 Lu-PSMA is feasible and can be considered for future assessment of optimal treatment sequence.

PSMA Radioligand Therapy in Prostate Cancer

“…PSA50, PSA-PFS and OS presented positive correlation with uptake in salivary glands either in a visual or quantitative scale ( P < 0.005), with good interreader reproducibility (k = 0.68). 40 Rahbar et al 41 published the interim analysis of 49 patients of the RALU retrospective trial. They found that a median of 6 doses of 223 Ra-RaCl 2 followed by 177 Lu-PSMA-617 is feasible with additional PSA30 decline in 29% and grade ≥3 AE occurring in 18% of mCRPC patients.…”

“…The median OS was 12.6 months and 31.4 months, respectively, after starting PSMA-RLT and 223 Ra-RaCl 2 ( P < 0.005), with a median interval of 9.3 months between studies. 41 Similar to the RALU study, Baumgarten et al 42 retrospectively evaluated 28 men with progressive mCRPC who received 177 Lu-PSMA-617 after 223 Ra-RaCl 2 administration. Patients with high bone tumor burden (>20 lesions) had a significantly shorter OS (14 vs 28 months, P < 0.045).…”

“…Rahbar et al 41 published the interim analysis of 49 patients of the RALU retrospective trial. They found that a median of 6 doses of 223 Ra-RaCl 2 followed by 177 Lu-PSMA-617 is feasible with additional PSA30 decline in 29% and grade ≥3 AE occurring in 18% of mCRPC patients.…”

“…They found that a median of 6 doses of 223 Ra-RaCl 2 followed by 177 Lu-PSMA-617 is feasible with additional PSA30 decline in 29% and grade ≥3 AE occurring in 18% of mCRPC patients. The median OS was 12.6 months and 31.4 months, respectively, after starting PSMA-RLT and 223 Ra-RaCl 2 ( P < 0.005), with a median interval of 9.3 months between studies 41 . Similar to the RALU study, Baumgarten et al 42 retrospectively evaluated 28 men with progressive mCRPC who received 177 Lu-PSMA-617 after 223 Ra-RaCl 2 administration.…”

A Retrospective Multicenter Analysis of the Incidence of Bone-Only Disease at PSMA PET/CT in Castration Resistant Prostate Cancer Patients

“…Patients with a high osseous metastatic burden in PSMA PET/CT have an overall worse prognosis and a higher risk of myelotoxicity when treated with 177Lutetium-PSMA-617 (Lu PSMA) [ 31 ]. However, the recent publication of an interim analysis of the RALU study shows the safety and feasibility of the sequential use of first Ra223 (Ra223 and then Lu PSMA [ 32 ], both myelotoxic therapies). Moreover, the findings from the WARMTH study showed that a prior therapy with 223Ra had a positive impact on overall survival in patients who were subsequently treated with LuPSMA [ 33 ].…”