177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study)

• Published in: European journal of nuclear medicine and molecular imaging Vol. 49; no. 3; pp. 1075 - 1085
• Main Authors: Khreish, Fadi, Ghazal, Zaidoon, Marlowe, Robert J., Rosar, Florian, Sabet, Amir, Maus, Stephan, Linxweiler, Johannes, Bartholomä, Mark, Ezziddin, Samer
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2022; Springer Nature B.V
• Subjects: Aged; Anemia; Antigens; Cardiology; Castration; Clinical trials; Confidence intervals; Data analysis; Dipeptides - adverse effects; Disease control; Heterocyclic Compounds, 1-Ring - adverse effects; Humans; Imaging; Lutetium; Lutetium - therapeutic use; Lutetium isotopes; Lymphopenia; Male; Median (statistics); Medicine; Medicine & Public Health; Metastases; Metastasis; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Patients; Prospective Studies; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - pathology; Prostatic Neoplasms, Castration-Resistant - radiotherapy; Radioisotopes; Radiology; Registries; Retrospective Studies; Safety; Statistical methods; Survival; Therapy; Thrombocytopenia; Treatment Outcome; Xerostomia; Prostate-specific membrane antigen (PSMA); Everyday practice; Lutetium-177-PSMA-617 radioligand therapy; Metastatic castration-resistant prostate cancer (mCRPC); “Real-world” data; LuPSMA-617 RLT; Lutetium-177-PSMA-617 radioligand therapy (177LuPSMA-617 RLT)
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-021-05525-7

Purpose
Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety and efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples treated in everyday practice.
Methods
We analyzed prospectively collected registry data regarding lutetium-177 (
177
Lu)-PSMA-617 RLT of 254 consecutive men with mCRPC seen in everyday academic practice. Since
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Lu-PSMA-617 was experimental salvage treatment following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated (median age 70 years; prior taxanes 74.0%, 188/254), with late–end-stage disease (visceral metastasis in 32.7%, 83/254). Primary endpoints were response to RLT, defined by changes from baseline serum prostate-specific antigen (PSA) concentration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with Kaplan–Meier statistics, and caregiver-reported and patient-reported safety. Unless noted, median (minimum–maximum) values are given.
Results
Patients received 3 (1–13)
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Lu-PSMA-617 activities (6.5 [2.5–11.6] GBq/cycle) every 5.7 (3.0–11.0) weeks. Best response was ≥ 50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confidence interval [95%CI] 4.4–6.6) months and OS, 14.5 (95%CI 11.5–17.5) months. In multivariable Cox proportional-hazards modeling, response to the initial ≤ 2 RLT administrations was the strongest significant prognosticator related to OS (hazard ratio 3.7 [95%CI 2.5–5.5],
p
 < 0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade 3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%). RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%).
Conclusions
In a large, prospectively observed “real-world” cohort with late-stage/end-stage mCRPC and conventional treatment failure,
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Lu-PSMA-617 RLT was effective, safe, and well-tolerated. Early biochemical disease control by such therapy was associated with better OS. Prospective study earlier in the disease course may be warranted.