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

Abstract Background 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. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [ 177 Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [ 177 Lu]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. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [ 177 Lu]Lu-PSMA I&T and five (9.1%) for [ 177 Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [ 177 Lu]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 [ 177 Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [ 177 Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion 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.