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Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer

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Abstract

Background

Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA) radioligand therapy is emerging as a promising treatment for metastatic castration-resistant prostate cancer refractory to established therapies. While there is an increasing body of survival and other data from retrospective analyses and prospective trials, there is no clear understanding of how best to predict therapy response and survival outcomes.

Objective

In this retrospective cohort analysis, we aimed to identify features that are associated with response to radioligand therapy and greater survival based on analysis of real-world data.

Patients and Methods

191 patients aged 70 ± 8 years with metastatic castration-resistant prostate cancer treated with radioligand therapy from November 2015 to February 2019 were included for analysis. Eligible patients had PSMA-expressing metastatic castration-resistant prostate cancer (confirmed by a 68Ga-PSMA-ligand positron emission tomography (PET)/computed tomography (CT) scan), an Eastern Cooperative Oncology Group performance status score ≤ 2 and no significant kidney, liver or bone marrow dysfunction (as characterised by kidney and liver function tests and a full blood count). Patients received one to five cycles of intravenous 177Lu-PSMA-ligand therapy. Endpoints included biochemical [prostate-specific antigen (PSA)] and radiologic (PSMA PET/CT) response, progression-free survival and overall survival, defined according to the Prostate Cancer Working Group 3 guidelines. Survival analysis was conducted by Kaplan–Meier estimation.

Results

Most individuals (89.5%) previously underwent first- and second-line systematic therapy. Of the 191 men treated with 452 cycles with mean injected activity of 6.1 ± 1.0 GBq per cycle, 159 patients were assessed for a biochemical response defined as a PSA decline ≥ 50% from baseline. A ≥ 50% PSA decline was observed in 89 (56%) patients, while any PSA decline occurred in 120 (75%) men. For the entire cohort, median values (interquartile range) of overall survival [n = 191], PSA progression-free survival [n = 132] and PET/CT progression-free survival were 12 (5–18), 4 (3–8) and 6 (3–10) months, respectively. Survival analysis confirmed better outcomes in individuals who had demonstrated therapy response. Predominantly lymph node metastatic disease and chemotherapy-naïve status were significant pre-therapy factors associated with longer survival. Baseline PSA was significantly linked to survival outcomes: lower levels predicted a lower risk of death and disease progression. Treatment-related adverse events included grade 3 or 4 haematological (12%), grade 1 or 2 renal (4.5%), and grade 3 or 4 clinical events (5.7%).

Conclusions

Our findings suggest that 177Lu-PSMA radioligand therapy provides a significant response rate with a low toxicity profile. The evidence promotes greater efficacy of radioligand therapy in predominantly lymph node metastatic castration-resistant prostate cancer, and in individuals with chemotherapy-naïve status and lower levels of baseline PSA.

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Acknowledgements

The authors thank Drs. Guiseppe Cardaci, David Macfarlane and Catherine Lucas for their care of patients included in this retrospective study. The permission granted by participants to use data for research and analysis purposes is gratefully acknowledged.

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Authors and Affiliations

  1. GenesisCare (Theranostics), East Fremantle, WA, Australia

    Danielle Meyrick, Marat Gallyamov, Shanthi Sabarimurugan, Nadia Falzone & Nat Lenzo

  2. Faculty of Health and Medical Sciences, Notre Dame University, Fremantle, WA, Australia

    Nat Lenzo

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  1. Danielle Meyrick
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  2. Marat Gallyamov
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Corresponding author

Correspondence to Danielle Meyrick.

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Funding

No external funding was used in the preparation of this article.

Conflict of Interest

Danielle Meyrick, Marat Gallyamoa, Shanthi Sabarimurugan, Nadia Falzone and Nat Lenzo have no conflicts of interest that are directly relevant to the content of this article.

Ethics Approval

The study was conducted in accordance with institutional ethical compliance for off-trial palliative treatment of patients with metastatic castration-resistant prostate cancer on a compassionate basis. From a regulatory perspective, this is provided under Category A of the Therapeutic Goods Administration Special Access Scheme.

Consent to Participate

Written informed consent for publication was obtained from all patients.

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Not applicable.

Availability of Data and Material

Data and material are available after request to the corresponding author.

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Not applicable.

Author Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Marat Gallyamov, Shanthi Sabarimurugan and Danielle Meyrick. The first draft of the manuscript was written by Marat Gallyamov and Danielle Meyrick, final editing performed by Nadia Falzone, Danielle Meyrick and Nat Lenzo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Meyrick, D., Gallyamov, M., Sabarimurugan, S. et al. Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer. Targ Oncol 16, 369–380 (2021). https://doi.org/10.1007/s11523-021-00801-w

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