Matched-pair analysis of [177Lu]Lu-PSMA I&T and [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.

Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC).

In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT.

A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [177Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [177Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared.

Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [177Lu]Lu-PSMA I&T and five (9.1%) for [177Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [177Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [177Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [177Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89).

In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.

European journal of nuclear medicine and molecular imaging. 2022 Mar 04 [Epub ahead of print]

Philipp E Hartrampf, Franz-Xaver Weinzierl, Andreas K Buck, Steven P Rowe, Takahiro Higuchi, Anna Katharina Seitz, Hubert Kübler, Andreas Schirbel, Markus Essler, Ralph A Bundschuh, Rudolf A Werner

Department of Nuclear Medicine, University Hospital Wuerzburg, Oberdürrbacherstraße 6, 97080, Würzburg, Germany. ., Department of Nuclear Medicine, University Hospital Wuerzburg, Oberdürrbacherstraße 6, 97080, Würzburg, Germany., Department of Radiology and Radiological Science, The Russell H Morgan, Johns Hopkins University School of Medicine, 601 N Caroline Str, Baltimore, MD, USA., Department of Urology and Paediatric Urology, University Hospital Wuerzburg, Oberdürrbacherstraße 6, 97080, Würzburg, Germany., Department of Nuclear Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

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