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177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with 177Lu-PSMA-617.

Methods

Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66–76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee.

Results

The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1–7) of 177Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9–6.3 GBq). The median follow-up was 24 weeks (IQR 15–36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level <220 U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28 weeks, p < 0.01, and 56 vs. 29 weeks, p = 0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18 weeks. Only ALP level <220 U/L was significantly associated with a longer PPFS (41 vs. 18 weeks, p < 0.01).

Conclusions

A PSA decline after the first cycle of 177Lu-PSMA-617 and an initial ALP level <220 U/L were predictors of a longer OS in patients with end-stage mCRPC. An ALP level <220 U/L was additionally associated with a longer PPFS.

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Acknowledgments

We thank the Radiochemistry Group at the Department of Nuclear Medicine for their highly reliable production of 177Lu-PSMA-617, and the nursing staff and the nuclear medicine technologists for their support.

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Correspondence to Kambiz Rahbar.

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Conflicts of interest

The University of Münster received consulting fees from ABX Advanced Biochemical Compounds, Radeberg, Germany for K.R. and M.B.

The authors declare they have no conflict of interest according the subject and matter of the presented article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not describe any studies with animals performed by any of the authors. This study was approved by the local ethics committee (no. 2016–585-f-S, Ethikkommission der Ärztekammer Westfalen-Lippe und der Westfälischen Wilhelms-Universität Münster).

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Bräuer, A., Grubert, L., Roll, W. et al. 177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 44, 1663–1670 (2017). https://doi.org/10.1007/s00259-017-3751-z

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  • DOI: https://doi.org/10.1007/s00259-017-3751-z

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