학술논문
Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.
Document Type
Academic Journal
Author
Sathekge MM; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa; Department of Nuclear Medicine, Steve Biko Academic Hospital, Pretoria, South Africa; Nuclear Medicine Research Infrastructure, Pretoria, South Africa. Electronic address: mike.sathekge@up.ac.za.; Lawal IO; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa; Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA.; Bal C; Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.; Bruchertseifer F; European Commission, Joint Research Centre, Karlsruhe, Germany.; Ballal S; Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.; Cardaci G; GenesisCare, Murdoch, WA, Australia.; Davis C; Department of Nuclear Medicine, Steve Biko Academic Hospital, Pretoria, South Africa.; Eiber M; Department of Nuclear Medicine, Klinikum Rechts Der Isar, Technical University of Munich and Bavarian Cancer Research Center (BZKF), Munich, Germany.; Hekimsoy T; Department of Nuclear Medicine, Klinikum Rechts Der Isar, Technical University of Munich and Bavarian Cancer Research Center (BZKF), Munich, Germany.; Knoesen O; Nuclear Technology Products (NTP), Division of the South African Nuclear Energy Cooperation (NECSA), Pelindaba, South Africa.; Kratochwil C; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Lenzo NP; GenesisCare, Murdoch, WA, Australia.; Mahapane J; Department of Radiography, University of Pretoria, Pretoria, South Africa.; Maserumule LC; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa; Department of Nuclear Medicine, Steve Biko Academic Hospital, Pretoria, South Africa; Nuclear Medicine Research Infrastructure, Pretoria, South Africa.; Mdlophane AH; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa; Nuclear Medicine Research Infrastructure, Pretoria, South Africa.; Mokoala KMG; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa; Department of Nuclear Medicine, Steve Biko Academic Hospital, Pretoria, South Africa; Nuclear Medicine Research Infrastructure, Pretoria, South Africa.; Ndlovu H; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa; Department of Nuclear Medicine, Steve Biko Academic Hospital, Pretoria, South Africa; Nuclear Medicine Research Infrastructure, Pretoria, South Africa.; Pant V; Royal Liverpool University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.; Rathke H; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany; Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Reed J; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa.; Sen IB; Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurugram, India.; Singh A; GenesisCare, Murdoch, WA, Australia.; Sood A; Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.; Tauber R; Department of Urology, School of Medicine, and Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.; Thakral P; Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurugram, India.; Yadav MP; Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.; Morgenstern A; Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa; European Commission, Joint Research Centre, Karlsruhe, Germany.
Source
Publisher: Lancet Pub. Group Country of Publication: England NLM ID: 100957246 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-5488 (Electronic) Linking ISSN: 14702045 NLM ISO Abbreviation: Lancet Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Actinium-225 ( 225 Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225 Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world.
Methods: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq225 Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 ( 177 Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival.
Findings: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of225 Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177 Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225 Ac-PSMA RLT. All patients who received more than seven cycles of 225 Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded.
Interpretation:225 Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events.
Funding: None.
Competing Interests: Declaration of interests MMS reports grants or contracts from Novartis; payment or honoraria from Bayer, Johnson & Johnson, NTP, and Sanofi; support for attending meetings from the International Atomic Energy Agency; and receipt of equipment or materials from POINT Biopharma. ME reports grants or contracts from Blue Earth Diagnostics; royalties from patent on radiohybrid PSMA; consulting fees from Novartis, Point Biopharma, payment from Novartis; payment for expert testimony from Novartis, Bayer, Telix, and Blue Earth Diagnostics; support for attending meetings from Blue Earth Diagnostics; and patent ownership on radiohybrid PSMA. TH reports grants or contracts from Siemens. CK reports patent ownership. NPL reports contracts from Telix, Ipsen/Ariceum, and Clarity; receipt of educational material from Telix; support for attending meetings from Telix; participation on the advisory board of Telix; and family stock ownership at Clarity. ASi reports support for attending meetings from Telix International, Australia and participation on Data Safety Monitoring Borad for Telix International. RT reports payment or honoraria from Astella, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck, MSD, Novartis, Orion, Pfizer, Roche, and Sanofi; support for attending meetings from Bayer, Janssen, Orion, Pfizer, and Roche; participation on Data Safety Monitoring Board or Advisory Board of Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eisei, EUSA, IPSEN, Janssen, Merck, MSD, Novartis, Orion, Pfizer, Philogen, Roche, and Sanofi; stock ownership at Bayer; and financial or non-financial interests at Thieme compliance and Elsevier. AM reports patents owning a patent for treatment of PSMA-expressing cancers. All other authors declare no competing interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Methods: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq
Findings: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of
Interpretation:
Funding: None.
Competing Interests: Declaration of interests MMS reports grants or contracts from Novartis; payment or honoraria from Bayer, Johnson & Johnson, NTP, and Sanofi; support for attending meetings from the International Atomic Energy Agency; and receipt of equipment or materials from POINT Biopharma. ME reports grants or contracts from Blue Earth Diagnostics; royalties from patent on radiohybrid PSMA; consulting fees from Novartis, Point Biopharma, payment from Novartis; payment for expert testimony from Novartis, Bayer, Telix, and Blue Earth Diagnostics; support for attending meetings from Blue Earth Diagnostics; and patent ownership on radiohybrid PSMA. TH reports grants or contracts from Siemens. CK reports patent ownership. NPL reports contracts from Telix, Ipsen/Ariceum, and Clarity; receipt of educational material from Telix; support for attending meetings from Telix; participation on the advisory board of Telix; and family stock ownership at Clarity. ASi reports support for attending meetings from Telix International, Australia and participation on Data Safety Monitoring Borad for Telix International. RT reports payment or honoraria from Astella, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck, MSD, Novartis, Orion, Pfizer, Roche, and Sanofi; support for attending meetings from Bayer, Janssen, Orion, Pfizer, and Roche; participation on Data Safety Monitoring Board or Advisory Board of Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eisei, EUSA, IPSEN, Janssen, Merck, MSD, Novartis, Orion, Pfizer, Philogen, Roche, and Sanofi; stock ownership at Bayer; and financial or non-financial interests at Thieme compliance and Elsevier. AM reports patents owning a patent for treatment of PSMA-expressing cancers. All other authors declare no competing interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)