Efficacy and haematologic toxicity of palliative radioligand therapy of metastatic castrate-resistant prostate cancer with lutetium-177-labeled prostate-specific membrane antigen in heavily pre-treated patients
Publication Details
Kesavan, M.,
Meyrick, D.,
Gallyamov, M.,
Turner, J. H.,
Yeo, S.,
Cardaci, G.,
&
Lenzo, N. P.
(2021).
Efficacy and haematologic toxicity of palliative radioligand therapy of metastatic castrate-resistant prostate cancer with lutetium-177-labeled prostate-specific membrane antigen in heavily pre-treated patients.
Diagnostics, 11 (3).
Abstract
Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (177Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative 177Lu-DOTAGA-(I-y)fk(Sub-KuE) (177Lu-PSMA I&T) with respect to efficacy and haematologic safety.
Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (68GaPSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed.
Results: One hundred patients completed one cycle of 177Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50–89), median number of prior therapies was three (1–6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (p < 0.0001; 95% CI: 0.08–0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated.
Conclusion: 177Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. 68Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.
Keywords
LuPSMA; mCRPC; hematologic toxicity; MDS
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