Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with (225)Ac-PSMA-617 targeted alpha-radiation therapy

Autor: Winald R. Gerritsen, Monika G. Looijen-Salamon, Inge M. van Oort, Leonie I. Kroeze, Uwe Haberkorn, Frank Bruchertseifer, Clemens Kratochwil, José A. E. Custers, Niven Mehra, Peter H.J. Slootbeek, Maarten J. van der Doelen, Alfred Morgenstern, Marcel J.R. Janssen, James Nagarajah
Rok vydání: 2021
Předmět:
Oncology
medicine.medical_specialty
Urology
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
030232 urology & nephrology
Castration resistant
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
urologic and male genital diseases
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Antigen
Internal medicine
Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15]
medicine
Clinical endpoint
Glutamate carboxypeptidase II
Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]
business.industry
medicine.disease
ddc
Women's cancers Radboud Institute for Health Sciences [Radboudumc 17]
030220 oncology & carcinogenesis
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
Cohort
Immunohistochemistry
business
Cohort study
Zdroj: Urologic Oncology-Seminars and Original Investigations, 39, 10, pp. 729.e7-729.e16
Urologic Oncology-Seminars and Original Investigations, 39, 729.e7-729.e16
ISSN: 1078-1439
Popis: Contains fulltext : 237645.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Targeted alpha-radiation therapy (TAT) with (225)Ac-labeled prostate-specific membrane antigen (PSMA) ligands is a promising novel treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. However, limited data are available on efficacy, quality of life (QoL), and pretherapeutic biomarkers. The aim of this study was to evaluate the efficacy of (225)Ac-PSMA TAT and impact on QoL in advanced mCRPC, and to explore predictive biomarkers on pretherapeutic metastatic tissue biopsies. METHODS: Observational cohort study including consecutive patients treated with (225)Ac-PSMA TAT between February 2016 and July 2018. Primary endpoint was overall survival (OS). Furthermore, prostate-specific antigen (PSA) changes, radiological response, safety, QoL, and xerostomia were evaluated. Biopsies were analyzed with immunohistochemistry and next-generation sequencing. RESULTS: Thirteen patients were included. Median OS was 8.5 months for the total cohort and 12.6 months for PSMA radioligand therapy-naïve patients. PSA declines of ≥90% and ≥50% were observed in 46% and 69% of patients, respectively. Six patients were radiologically evaluable; 50% showed partial response. All patients showed >90% total tumor volume reduction on PET imaging. Patients experienced clinically relevant decrease of pain and QoL improvement in physical and role functioning domains. Xerostomia persisted during follow-up. Patients with high baseline immunohistochemical PSMA expression or DNA damage repair alterations tended to have longer OS. CONCLUSIONS: TAT with (225)Ac-PSMA resulted in remarkable survival and biochemical responses in advanced mCRPC patients. Patients experienced clinically relevant QoL improvement, although xerostomia was found to be nontransient. Baseline immunohistochemical PSMA expression and DNA damage repair status are potential predictive biomarkers of response to (225)Ac-PSMA TAT.
Databáze: OpenAIRE
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