Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer(Figure presented.)

Matthias M. Heck, Robert Tauber, Sebastian Schwaiger, Margitta Retz, Calogero D'Alessandria, Tobias Maurer, Andrei Gafita, Hans Jürgen Wester, Jürgen E. Gschwend, Wolfgang A. Weber, Markus Schwaiger, Karina Knorr, Matthias Eiber

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

Abstract

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly being used in metastatic castration-resistant prostate cancer (mCRPC). The objective of this study is to report our clinical experience with RLT using 177-lutetium–labeled PSMA-I&T. A total of 100 patients were treated under a compassionate use protocol with a total number of 319 cycles (median two cycles, range 1–6). Eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy or chemoineligibility, and positive PSMA-ligand uptake at positron-emission tomography scan. The 177Lu-PSMA-I&T was given 6–8 weekly with an activity of 7.4 GBq up to six cycles. The median number of previous mCRPC regimens was 3 (range 1–6), and 35 patients had visceral metastases. Prostate-specific antigen decline of ≥50% was achieved in 38 patients, median clinical progression-free survival (cPFS) was 4.1 mo, and median overall survival (OS) was 12.9 mo. Subgroup analyses identified an association of visceral metastases with a poor prostate-specific antigen (PSA) response and shorter cPFS and OS, and an association of rising lactate dehydrogenase (LDH) with shorter cPFS and OS. Patients achieving PSA decline of ≥50% within 12 wk of treatment showed longer cPFS and OS. Treatment-emergent hematologic grade 3/4 toxicities were anemia (9%), thrombocytopenia (4%), and neutropenia (6%). Grade 3/4 nonhematologic toxicities were not observed. RLT with 177Lu-PSMA-I&T showed good activity in more than one-third of patients with late-stage mCRPC at low toxicity. Presence of visceral metastases and rising LDH were associated with worse treatment outcome. Patient summary: We analyzed the treatment outcome and toxicity of prostate-specific membrane antigen–targeted radioligand therapy in patients with metastatic castration-resistant prostate cancer. We found that a good treatment response could be achieved in a subgroup of patients with few side effects. We also observed that treatment outcome was worse in patients with organ metastases and elevated lactate dehydrogenase in blood tests. Radioligand therapy with 177Lu-PSMA-I&T showed good activity in more than one-third of patients with late-stage metastatic castration-resistant prostate cancer at low toxicity. Presence of visceral metastases and rising lactate dehydrogenase were associated with worse treatment outcome.

Original languageEnglish
Pages (from-to)920-926
Number of pages7
JournalEuropean Urology
Volume75
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Lutetium
  • Metastatic castration-resistant prostate cancer
  • Prostate-specific membrane antigen
  • Radioligand therapy

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