Experience of rescue therapy with [177Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [177Lu]Lu-PSMA-I&T

  • Purpose Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T. Methods Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4–8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from firstPurpose Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T. Methods Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4–8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application. Results Despite progression with [177Lu]Lu-PSMA-I&T, after the first cycle of [177Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [177Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [177Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [177Lu]Lu-PSMA-I&T therapy but showed an immediate response to [177Lu]Lu-rhPSMA-10.1. The additional treatment with [177Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients. Conclusions Patients showing tumour progression while receiving [177Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [177Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [177Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.show moreshow less

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Metadaten
Author:Alexander Gäble, Alexander DierksGND, Andreas Rinscheid, Marianne Patt, Georgine Wienand, Christian H. Pfob, Malte Kircher, Kazuhito Fukushima, Ana Antić Nikolić, Johanna S. Enke, Tilman Janzen, Julie Steinestel, Hildegard Kempter, Martin TrepelGND, Dorothea WeckermannGND, Constantin LapaORCiDGND, Ralph A. Bundschuh
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/117126
ISSN:1619-7070OPAC
ISSN:1619-7089OPAC
Parent Title (English):European Journal of Nuclear Medicine and Molecular Imaging
Publisher:Springer Science and Business Media LLC
Place of publication:Berlin
Type:Article
Language:English
Year of first Publication:2024
Publishing Institution:Universität Augsburg
Release Date:2024/11/29
DOI:https://doi.org/10.1007/s00259-024-06959-5
Institutes:Medizinische Fakultät
Medizinische Fakultät / Universitätsklinikum
Medizinische Fakultät / Lehrstuhl für Innere Medizin mit Schwerpunkt Hämatologie und Onkologie
Medizinische Fakultät / Lehrstuhl für Nuklearmedizin
Medizinische Fakultät / Lehrstuhl für Psychiatrie und Psychotherapie
Medizinische Fakultät / Lehrstuhl für Urologie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Latest Publications (not yet published in print):Aktuelle Publikationen (noch nicht gedruckt erschienen)
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)