ASCO 2022: Safety and Survival Outcomes in Patients With mCRPC Treated With 177Lu-PSMA After Radium-223: Interim Analysis of the RALU Study

( At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Prostate, Testicular, and Penile cancers on Monday afternoon included a presentation from Dr. Kambiz Rahbar discussing sequential treatment with lutetium-177–prostate-specific membrane antigen (177Lu-PSMA) after radium-223 (223Ra) in men with metastatic castration-resistant prostate cancer (mCRPC).

There has been significant interest recently in the field of theranostics for prostate cancer. The phase II TheraP and phase III VISION trials demonstrated the benefit of 177Lu-PSMA-617 in patients with heavily pre-treated mCRPC. However, prior to this, the ALSYMPCA trial demonstrated an overall survival benefit to the use of the bone-trophic radio-emitter radium-223. Previous data from the observational REASSURE and WARMTH studies suggested that it may be feasible to sequencing there two agents. In this abstract, the authors sought to further examine the safety and clinical outcomes of sequential 223Ra/177Lu-PSMA therapy in men with mCRPC.

To do so, they used data from the observational, retrospective RALU study across a number of German centers. They examined baseline characteristics, safety (primary endpoint) and OS (secondary endpoint) outcomes among men who received 177Lu-PSMA after 223Ra.

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They were able to identify 49 patients to date. Prior to starting 177Lu-PSMA, 73% of patients were Eastern Cooperative Oncology Group performance status (ECOG PS) 1 and 27% ECOG PS 2. Visceral metastases were present in 31% of men and the median prostate-specific antigen (PSA) and alkaline phosphatase (ALP) were 287 ng/ml and 142 U/L, respectively.

The majority (70%) of patients had received 4 or more life-prolonging therapies prior to 177Lu-PSMA, with abiraterone acetate (80%), enzalutamide (67%) and docetaxel (92%) being the most frequently used. Further, nearly three-quarters (74%) of patients received 5 or more 223Ra injections.

Patients received either PSMA-617 (67%) or PSMA I&T (33%). Most patients (65%) received 1–4 cycles and with the remaining 33% received 5–6 cycles. The median duration of 177Lu-PSMA therapy was 4.9 months (0–57.1) and the median time from the last 223Ra dose to first 177Lu-PSMA dose was 9.3 months (0.9–41.9).

Any grade treatment-emergent adverse events (TEAEs) from the start of 177Lu-PSMA therapy to 30 days of follow-up occurred in 91.8% of patients with serious TEAEs noted 20% of patients. Grade 3-4 hematologic laboratory abnormalities up to 90 days post-177Lu-PSMA occurred in 34.7% of patients for anemia, 12.8% for thrombocytopenia and 2.0% for neutropenia. No grade 5 toxicities occurred.

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39% of patients had ≥30% decline in PSA during 177Lu-PSMA treatment. The median OS was 12.6 months (95% CI 8.8–16.1) from the start of 177Lu-PSMA therapy and 31.4 months (95%CI 25.7-37.6) from the start of 223Ra.

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Thus, the authors conclude that these real world data demonstrate the feasibility of sequential treatment with 223Ra and 177Lu-PSMA in selected patients with advanced mCRPC.

Presented by: Kambiz Rahbar, MD, Department of Nuclear Medicine, University Hospital Münster, Münster, Germany