[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study

Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antige...

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Bibliographic Details
Published in:The lancet oncology 2018-06, Vol.19 (6), p.825-833
Main Authors: Hofman, Michael S, Violet, John, Hicks, Rodney J, Ferdinandus, Justin, Thang, Sue Ping, Akhurst, Tim, Iravani, Amir, Kong, Grace, Ravi Kumar, Aravind, Murphy, Declan G, Eu, Peter, Jackson, Price, Scalzo, Mark, Williams, Scott G, Sandhu, Shahneen
Format: Article
Language:English
Subjects:
Acetic acid
Aged
Androgens
Bone imaging
Bone tumors
Cancer therapies
Castration
Chemotherapy
Clinical trials
Computed tomography
Dipeptides - administration & dosage
Dipeptides - adverse effects
Disease Progression
Fatigue
Fractures
Health Status
Heterocyclic Compounds, 1-Ring - administration & dosage
Heterocyclic Compounds, 1-Ring - adverse effects
Humans
Intravenous administration
Kallikreins - blood
Liver
Lutetium - administration & dosage
Lutetium - adverse effects
Male
Medical research
Metastases
Metastasis
Nausea
Neoplasm Metastasis
Pain
Patients
Positron emission tomography
Prospective Studies
Prostate cancer
Prostate-Specific Antigen - blood
Prostatic Neoplasms, Castration-Resistant - blood
Prostatic Neoplasms, Castration-Resistant - diagnostic imaging
Prostatic Neoplasms, Castration-Resistant - pathology
Prostatic Neoplasms, Castration-Resistant - radiotherapy
Quality of Life
Radioactivity
Radioisotopes - administration & dosage
Radioisotopes - adverse effects
Radiopharmaceuticals - administration & dosage
Radiopharmaceuticals - adverse effects
Solid tumors
Studies
Thrombocytopenia
Time Factors
Toxicity
Treatment Outcome
Tumors
Victoria
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Summary:Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments. In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583. Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37–75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(18)30198-0