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[177Lu]Lu-PSMA-617 as first-line systemic therapy in patients with metastatic castration-resistant prostate cancer: a real-world study

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

Abstract

Purpose

The use of [177Lu]Lu-PSMA-617 radioligand therapy has become increasingly recognized as a viable therapeutic approach for patients in the advanced stages of metastatic castration-resistant prostate cancer (mCRPC). However, there is limited data regarding its effectiveness and safety in earlier lines. This study aims to present our institution’s experience with [177Lu]Lu-PSMA-617 as a first-line systemic therapy for mCRPC.

Methods

We collected and analyzed data from consecutive mCRPC patients who underwent first-line treatment with [177Lu]Lu-PSMA-617 at our center from 2015 to 2023. The various outcome measures included best prostate-specific antigen-response rate (PSA-RR) (proportion of patients achieving a ≥ 50% decline in PSA); objective radiographic response rate (ORR) (proportion of patients achieving complete or partial radiographic responses); radiographic progression-free survival (rPFS) (measured from treatment initiation until radiographic progression or death from any cause); overall survival (OS) (measured from treatment initiation until death from any cause); and adverse events.

Results

Forty treatment-naïve mCRPC patients with PSMA-positive disease on [68Ga]Ga-PSMA-11 PET/CT were included (median age: 68.5 years, range: 45–78; median PSA: 41 ng/mL, range: 1-3028). These patients received a median cumulative activity of 22.2 GBq (range: 5.55–44.4) [177Lu]Lu-PSMA-617 over 1–6 cycles at 8–12 week intervals. A ≥ 50% decline in PSA was observed in 25/40 (62.5%) patients (best PSA-RR). Radiographic responses were evaluated for thirty-eight patients, with thirteen showing partial responses (ORR 34.2%). Over a median follow-up of 36 months, the median rPFS was 12 months (95% confidence interval, CI: 9–15), and the median OS was 17 months (95% CI: 12–22). Treatment-emergent grade ≥ 3 anemia, leucopenia, and thrombocytopenia were noted in 4/40 (10%), 1/40 (2.5%), and 3/40 (7.5%) patients, respectively.

Conclusion

The findings suggest that [177Lu]Lu-PSMA-617 is a safe and effective option as a first-line treatment in mCRPC. Further trials are needed to definitively establish its role as an upfront treatment modality in this setting.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Swayamjeet Satapathy, Madhav Prasad Yadav, Sanjana Ballal & Chandrasekhar Bal

  2. Department of Medical Oncology, B.R. Ambedkar Institute Rotary Cancer Hospital (B.R.A.I.R.C.H.), All India Institute of Medical Sciences, New Delhi, 110029, India

    Ranjit Kumar Sahoo

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  1. Swayamjeet Satapathy
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Contributions

Drs. Satapathy and Bal conceived the idea; Drs. Satapathy, Yadav, Ballal, and Sahoo collected the data; Drs. Satapathy, and Ballal analyzed the data; Dr. Satapathy wrote the initial draft of the manuscript; Drs. Yadav and Ballal modified the manuscript; Drs. Sahoo and Bal critically reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chandrasekhar Bal.

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Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institute Ethics Committee, All India Institute of Medical Sciences, New Delhi (Ref. No. IESC/T-229/05.05.2015, RT-46/2015).

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

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Satapathy, S., Yadav, M., Ballal, S. et al. [177Lu]Lu-PSMA-617 as first-line systemic therapy in patients with metastatic castration-resistant prostate cancer: a real-world study. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06677-y

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