Maarten J van der Doelen1, Niven Mehra2, Inge M van Oort3, Monika G Looijen-Salamon4, Marcel J R Janssen5, José A E Custers6, Peter H J Slootbeek2, Leonie I Kroeze4, Frank Bruchertseifer7, Alfred Morgenstern7, Uwe Haberkorn8, Clemens Kratochwil8, James Nagarajah9, Winald R Gerritsen2. 1. Radboud University Medical Center, Department of Medical Oncology, Nijmegen, The Netherlands; Radboud University Medical Center, Department of Urology, Nijmegen, The Netherlands. Electronic address: Maarten.vanderDoelen@radboudumc.nl. 2. Radboud University Medical Center, Department of Medical Oncology, Nijmegen, The Netherlands. 3. Radboud University Medical Center, Department of Urology, Nijmegen, The Netherlands. 4. Radboud University Medical Center, Department of Pathology, Nijmegen, The Netherlands. 5. Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen, The Netherlands. 6. Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Medical Psychology, Nijmegen, The Netherlands. 7. European Commission, Joint Research Centre, Nuclear Safety and Security, Karlsruhe, Germany. 8. University Hospital Heidelberg, Department of Nuclear Medicine, Germany. 9. Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen, The Netherlands; Technical University Munich, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich, Germany.
Abstract
INTRODUCTION: Targeted alpha-radiation therapy (TAT) with 225Ac-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 225Ac-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 225Ac-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 225Ac-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 225Ac-PSMA TAT.
INTRODUCTION: Targeted alpha-radiation therapy (TAT) with 225Ac-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 225Ac-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 225Ac-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 225Ac-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 225Ac-PSMA TAT.
Authors: Mike M Sathekge; Frank Bruchertseifer; Mariza Vorster; Alfred Morgenstern; Ismaheel O Lawal Journal: Eur J Nucl Med Mol Imaging Date: 2021-06-26 Impact factor: 9.236