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

• DOI: 10.1007/s00259-021-05525-7
• Publication Date: 2021-09-07T16:03:06Z
• Authors: Fadi Khreish; Zaidoon Ghazal; Robert J. Marlowe; Florian Rosar; Amir Sabet; Stephan Maus; Johannes Linxweiler; Mark Bartholomä; Samer Ezziddin
• Keywords: Male; Metastatic castration-resistant prostate cancer (mCRPC); Lutetium-177-PSMA-617 radioligand therapy (177LuPSMA-617 RLT); Heterocyclic Compounds, 1-Ring/adverse effects [MeSH] ; Prostatic Neoplasms, Castration-Resistant/pathology [MeSH] ; Aged [MeSH] ; Humans [MeSH] ; Prospective Studies [MeSH] ; Prostate-Specific Antigen [MeSH] ; Treatment Outcome [MeSH] ; Retrospective Studies [MeSH] ; Everyday practice ; Lutetium/therapeutic use [MeSH] ; Original Article ; Metastatic castration-resistant prostate cancer (mCRPC) ; Lutetium-177-PSMA-617 radioligand therapy ( ; Male [MeSH] ; “Real-world” data ; Dipeptides/adverse effects [MeSH] ; Radioisotopes [MeSH] ; Prostate-specific membrane antigen (PSMA) ; Registries [MeSH] ; Prostatic Neoplasms, Castration-Resistant/radiotherapy [MeSH]; 610; Lutetium; Everyday practice; Heterocyclic Compounds, 1-Ring; 03 medical and health sciences; 0302 clinical medicine; Humans; Prospective Studies; Registries; Aged; Retrospective Studies; Radioisotopes; ddc:610; ���Real-world��� data; Dipeptides; “Real-world” data; Prostate-Specific Antigen; 3. Good health; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome; Prostate-specifc membrane antigen (PSMA); Original Article

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