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Radionuklidtherapie mit PSMA-Liganden bei fortgeschrittenem Prostatakarzinom

PSMA radioligand therapy in patients with advanced prostate cancer

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Zusammenfassung

Hintergrund

Das metastasierte kastrationsresistente Prostatakarzinom (mCRPC) kann durch Fortschritte in den letzten Jahren immer besser behandelt werden. Hierbei kommen Substanzen zum Einsatz, die effektiv die Androgenrezeptorachse blockieren, verschiedene Chemotherapeutika sowie das Radiopharmakon 223Radium. Trotzdem kommt es regelhaft zu primärer und sekundärer Resistenzbildung gegen sämtliche Therapieoptionen. Daher werden neue Therapieansätze dringend benötigt. Die 177Lutetium-PSMA- (prostataspezifisches Membranantigen‑)Radioligandentherapie (177Lu-PSMA-RLT) stellt eine gute Reserveoption dar, welche bei noch fehlender Zulassung in individuellen Heilversuchen mit vielversprechenden Erfolgen eingesetzt werden kann.

Fragestellung

In diesem Beitrag wird eine Standortbestimmung der 177Lu-PSMA-RLT beim mCRPC 2020 beschrieben.

Material und Methode

Die Therapielandschaft beim mCRPC und der aktuellen Evidenz der 177Lu-PSMA-RLT nach PubMed-Recherche werden dargestellt.

Ergebnisse

In verschiedenen, teils umfangreichen retrospektiven Arbeiten und in ersten prospektiven Studien zeigt sich die 177Lu-PSMA-RLT bei einem Teil der Patienten als vielversprechende Reservetherapie. Das Toxizitätsprofil stellt sich auch im Vergleich zu anderen Therapieoptionen beim mCRPC als günstig dar. Die Phase-III-Zulassungsstudie VISION ist weit fortgeschritten und könnte zur Zulassung der 177Lu-PSMA-RLT in Kombination mit Abirateron oder Enzalutamid nach Vorbehandlung mit Enzalutamid oder Abirateron und Chemotherapie mit Docetaxel führen.

Schlussfolgerung

Trotz der hoffnungsvollen Ansätze müssen die Ergebnisse der VISION-Studie vor dem breiten Einsatz der 177Lu-PSMA-RLT abgewartet werden. Bis dahin sollten nur Patienten im Sinne von individuellen Heilversuchen und den hierzu geltenden Regeln behandelt werden.

Abstract

Background

Based on significant progress in recent years, metastatic castration-resistant prostate cancer (mCRPC) patients can be treated better and better. The medications include androgen signaling inhibitors, chemotherapy, 223Ra, and sipuleucel-T. Most patients treated with these agents will still develop primary or secondary resistance against any given drug. The 177Lutetium-PSMA radioligand therapy (177Lu-PSMA-RLT) represents a good reserve option and can be used within compassionate use provisions demonstrating promising efficacy in the majority of patients in Germany.

Objectives

Establishment of status quo of 177Lu-PSMA-RLT in mCRPC in 2020.

Materials and methods

Presentation of the therapy landscape in mCRPC and the current evidence on 177Lu-PSMA-RLT after PubMed based literature search.

Results

Several larger retrospective studies and the first prospective trials on 177Lu-PSMA-RLT show premature but encouraging evidence on 177Lu-PSMA-RLT to be a promising new option in mCRPC patients. The toxicity profile seems to be favorable. The phase III trial VISION aims to provide evidence for the approval of 177Lu-PSMA-RLT in combination with abiraterone or enzalutamide in patients having been pretreated with enzalutamide or abiraterone and docetaxel.

Conclusions

Despite the promising preliminary results of 177Lu-PSMA-RLT, the efficacy results of VISION need to be awaited prior to using the therapy outside of compassionate use provisions.

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Abbreviations

177Lu-PSMA-RLT:

177Lutetium dotierte PSMA-Radioligandentherapie

ARTA:

„Androgen receptor targeted agent“

CTCAE:

„Common terminology criteria of adverse events“

LHRH:

Luteinisierendes Hormon Releasing-Hormon

mAb:

Monoklonaler Antikörper

mCRPC:

Metastasiertes kastrationsresistentes Prostatakarzinom

OS:

Gesamtüberleben

PCWG3:

„Prostate cancer working group 3“

PFS:

Progressionsfreies Überleben

PSA:

Prostataspezifisches Antigen

PSA50:

PSA-Abfall um mindestens 50 %

PSMA:

Prostataspezifisches Membranantigen

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Author information

Authors and Affiliations

  1. Klinik für Urologie und Kinderurologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1 GB A1, 48149, Münster, Deutschland

    M. Bögemann

  2. Klinik für Nuklearmedizin, Universitätsklinikum Essen, Essen, Deutschland

    K. Herrmann

  3. Klinik für Urologie, Universitätsklinikum Essen, Essen, Deutschland

    J. P. Radtke

  4. Klinik für Nuklearmedizin, Universitätsklinikum Münster, Münster, Deutschland

    K. Rahbar

  5. Westdeutsches Tumorzentrum, Universitätsklinikum Essen, Essen, Deutschland

    M. Bögemann, K. Herrmann, J. P. Radtke & K. Rahbar

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  1. M. Bögemann
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  4. K. Rahbar
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Correspondence to M. Bögemann.

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Interessenkonflikt

M. Bögemann, K. Herrmann, J.P. Radtke und K. Rahbar geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Bögemann, M., Herrmann, K., Radtke, J.P. et al. Radionuklidtherapie mit PSMA-Liganden bei fortgeschrittenem Prostatakarzinom. Urologe 59, 680–686 (2020). https://doi.org/10.1007/s00120-020-01205-w

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  • DOI: https://doi.org/10.1007/s00120-020-01205-w

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