1629P - Lutetium-177–prostate-specific membrane antigen (177Lu-PSMA) therapy in patients (pts) with prior Radium-223 (223Ra)

Background

The safety and efficacy of sequential use of ²²³Ra and ¹⁷⁷Lu-PSMA in pts with metastatic castration-resistant prostate cancer (mCRPC) were assessed in a real-world study (RaLu) conducted across multiple centres in Germany and Israel.

Methods

Data were collected from multiple centres in Germany (2021–2022) and Israel (2022–2023) pertaining to patients with mCRPC who had received ≥1 ²²³Ra dose and, in any subsequent therapy line, ≥1 ¹⁷⁷Lu-PSMA dose.

Results

Data from 198 pts were analysed. At the start of ¹⁷⁷Lu-PSMA therapy, the median age was 73 years and 20% of pts had visceral disease. The median prostate-specific antigen (PSA) level was 239.5 ng/ml and median alkaline phosphatase (ALP) level was 143.0 U/L. Overall, 58% of pts had received ≥4 life-prolonging therapies before starting ¹⁷⁷Lu-PSMA. All pts had received ²²³Ra (66% had received six ²²³Ra injections). Other prior treatments included abiraterone (75%), enzalutamide (75%), docetaxel (70%) and cabazitaxel (29%). Overall, 38% of pts had received ≥4 ¹⁷⁷Lu-PSMA cycles, with a median completion of 3 cycles. Safety is summarised in the table. Treatment-emergent adverse events (TEAEs) with ¹⁷⁷Lu-PSMA were mainly haematological and non-fatal. Excluding laboratory abnormalities, the most common (≥10% of pts) any-grade TEAEs were dry mouth (12%) and asthenia (11%). PSA data were available for 102 pts during ¹⁷⁷Lu-PSMA treatment; a PSA decline of ≥30% or ≥50% occurred in 48 (47%) and 38 (37%) pts, respectively. Corresponding ALP declines occurred in 13 (17%) and 6 (8%) of 77 pts. Median overall survival was 12.0 months (95% CI, 10.5–15.1) from the start of ¹⁷⁷Lu-PSMA and 33.4 months (95% CI, 31.4–37.3) from the start of ²²³Ra. Table: 1629P

TEAEs and grade 3–4 laboratory abnormalities during ¹⁷⁷Lu-PSMA therapy

N, number of pts per group; n, number of pts with specified event; TEAE, treatment-emergent adverse events.^aFrom starting ¹⁷⁷Lu-PSMA to the end of 30-day follow-up.^bUp to 90 days after last ¹⁷⁷Lu-PSMA dose.

Conclusions

These real-world findings support the clinical feasibility of treating pts with mCRPC with ¹⁷⁷Lu-PSMA following treatment with ²²³Ra. These insights may provide valuable guidance for optimising treatment sequencing and decision-making in clinical practice.

Clinical trial identification

Editorial acknowledgement

Dr Chris Guise of Cancer Communications and Consultancy Ltd., UK, provided medical writing assistance (funded by Bayer).

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Disclosure

K. Rahbar: Financial Interests, Personal, Other, Honoraria: Advanced accelerator applications, Bayer, ABX GmbH, ABX-CRO, Novartis, UroTrials, Pharmtrace, AMGEN, Janssen-Cilag. M. Sarfaty: Financial Interests, Personal, Other, Honoraria: BMS, MSD, Janssen, Astellas, Pfizer, Novartis, Lilly, Eisai, Merck; Financial Interests, Personal, Advisory Board: Astellas, Regeneron, Merck, Pfizer. R. Leibowitz: Financial Interests, Personal, Advisory Board: Bayer. M. Eiber: Financial Interests, Personal, Stocks or ownership: Novartis, Telix Pharmaceuticals; Financial Interests, Personal, Advisory Board: Blue Earth Diagnostics, ABX Advanced biochemical compounds, Janssen Oncology, Telix Pharmaceuticals, Novartis; Financial Interests, Institutional, Research Funding: Siemens, ABX Advanced biochemical compounds, Blue Earth Diagnostics; Financial Interests, Personal, Other, Patent application: rhPSMA; Financial Interests, Institutional, Sponsor/Funding: Bayer; Financial Interests, Personal, Other, Travel expenses: Bayer Schering Pharma. C. la Fougère: Financial Interests, Personal, Advisory Board: Bayer, Novartis, EUSA-Pharma, Ipsen, Onco design, Sirtex Medical; Financial Interests, Institutional, Research Funding: Oncovision, Siemens Healthineers. V. Prasad: Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications; Financial Interests, Personal, Advisory Board: Bayer, Telix Pharmaceuticals, Curium; Financial Interests, Institutional, Research Funding: Ipsen. W.P. Fendler: Financial Interests, Personal, Other, Honoraria: Parexel, Advanced Accelerator Applications; Financial Interests, Personal, Advisory Board: Janssen, Calyx, Bayer; Financial Interests, Institutional, Research Funding: Sofie. H. Dittmann: Financial Interests, Personal, Advisory Board: Bayer, Ipsen, Eisai AG. R.A. Bundschuh: Financial Interests, Personal, Other, Honoraria: Eisai AG; Financial Interests, Personal, Advisory Board: Bayer. K.M. Pabst: Financial Interests, Personal and Institutional, Other, Clinician Scientist Stipend of the University Medicine Essen Clinician Scientist Academy: Faculty of Medicine and Deutsche Forschungsgemeinschaft; Financial Interests, Institutional, Research Funding: Bayer; Financial Interests, Personal, Other, Travel expenses: Ipsen, Novartis; Financial Interests, Personal, Other, Consultancy: Novartis. M. Kurtinecz, M. Korn: Financial Interests, Personal, Full or part-time Employment: Bayer. M. Essler: Financial Interests, Personal, Advisory Board: Bayer, Advanced Accelerator Applications, Ipsen; Financial Interests, Personal, Other, Travel expenses: Ipsen. O. Sartor: Financial Interests, Personal, Advisory Board: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant Sciences, Myriad genetics, Novartis, Clarity Pharmaceuticals, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, Noxopharm, Clovis Oncology, Noria Therapeutics, Point biopharma, TeneoBio, Telix Pharmaceuticals, Theragnostics; Financial Interests, Personal, Other, Travel expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Stocks or ownership: Lilly, GSK, AbbVie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Clovis Oncology; Financial Interests, Institutional, Research Funding: Bayer, Sanofi, Endocyte, Merck, InVitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, AstraZeneca, Dendreon, SOTIO, Janssen, Progenics. All other authors have declared no conflicts of interest.