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Outcome and safety of rechallenge [177Lu]Lu-PSMA-617 in patients with metastatic prostate cancer

  • Anna Yordanova
  • Paula Linden
  • Stefan Hauser
  • Michael Meisenheimer
  • Stefan Kürpig
  • Georg Feldmann
  • Florian C. Gaertner
  • Markus Essler
  • Hojjat AhmadzadehfarEmail author
Original Article

Abstract

Background

Data are sparse regarding the feasibility of radioligand therapy (RLT) with [177Lu]Lu-PSMA-617 as a retreatment. We aimed to assess the outcome and safety of rechallenge PSMA-RLT in patients with progressive prostatic cancer who previously benefited from this therapy.

Materials and methods

Patients who received rechallenge therapy at our department from January 2015 to March 2018 were assessed. Non-haematological and haematological adverse events were evaluated from laboratory data and clinical reports and were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Time to prostate-specific-antigen (PSA) progression and the overall survival (OS) rate of the study patients were calculated from the date of the first rechallenge cycle. Furthermore, the OS calculated from the first cycle baseline PSMA-RLT was compared with the survival of patients who received only baseline PSMA-RLT. The response data were determined using [68Ga]Ga-PSMA-PET/CT and measurements of the tumour marker PSA.

Results

Included in this retrospective study were 30 patients who were initially treated with a median of 3 cycles (range 1–5) of PSMA-RLT and were eventually retreated after a median of 6 months (range 2–26). Each patient received a median of 3 (range 1–6) rechallenge cycles. None of the patients experienced a disabling or life-threatening grade 4 adverse event according to the Common Toxicity Criteria (CTC). Grade 3 toxicity occurred in 8 patients (27%). Serious adverse events included leucopoenia (n = 2), neutropoenia (n = 1), anaemia (n = 4), thrombopenia (n = 4) and elevated renal parameters (n = 1). Irreversible adverse events occurred in 21 patients (70%). The permanent adverse events were mild/moderate (CTC grade 1/2) in 19 patients and serious (CTC grade 3) in two patients, respectively. According to PSA measurements, 75–90% of patients showed a benefit (response/stable) from the first 4 rechallenge cycles. The median OS was 12 months calculated from the first rechallenge cycle and 25 months calculated from the first cycle baseline PSMA-RLT. For comparison, the median OS in patients who received only baseline PSMA-RLT was 9 months. The difference according to the logrank test was significant: p value <0.001. Patients with a PSA decrease after the first cycle of rechallenge PSMA-RLT survived a median of 19 months, while patients with a PSA increase survived only 6 months.

Conclusion

Rechallenge prostate-specific membrane antigen (PSMA) therapy has an acceptable safety profile. The majority of the retreated patients benefited from the rechallenge therapy. Patients who showed a biochemical response achieved a longer OS compared to patients who did not respond. The median OS was significantly longer in patients after rechallenge PSMA-RLT than in patients who received only baseline PSMA-RLT.

Keywords

Recurrence PSMA Lutetium-177 Prostate cancer CRPC Radioligand therapy 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no financial or non-financial competing interests.

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.

Informed consent

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

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Anna Yordanova
    • 1
  • Paula Linden
    • 1
  • Stefan Hauser
    • 2
  • Michael Meisenheimer
    • 1
  • Stefan Kürpig
    • 1
  • Georg Feldmann
    • 3
  • Florian C. Gaertner
    • 1
  • Markus Essler
    • 1
  • Hojjat Ahmadzadehfar
    • 1
    Email author
  1. 1.Department of Nuclear MedicineUniversity Hospital BonnBonnGermany
  2. 2.Department of UrologyUniversity Hospital BonnBonnGermany
  3. 3.Department of Internal Medicine 3University Hospital BonnBonnGermany

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