Experience of rescue therapy with [177Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [177Lu]Lu-PSMA-I&T
Year: 2024
Type: article
Abstract: 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 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. Graphical Abstract
Authors: Alexander Gäble, Alexander Dierks, 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 Trepel, Dorothea Weckermann, Constantin Lapa, Ralph A. Bundschuh
Institutions: University of Augsburg, University Hospital Augsburg
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
OpenAlex ID: W4404016608