Clinical outcomes of prompt versus deferred
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Lu-PSMA-617 initiation for metastatic castration-resistant prostate cancer (mCRPC) based on prior androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy exposure: A real-world prostate cancer disease observation (PRECISION) data platform analysis.
Authors: Sartor Alton Oliver , Wei Xiao X. , Shore Neal D. , Heath Elisabeth I. , Nguyen Jennifer , Patel Jeetvan , Sawhney Amrita , Kang Barinder , Byrne Clare , Tang Jackson , George Daniel J. 
Published: February 2025

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Background:
The broad therapeutic arsenal for mCRPC, with overlapping indications, makes selecting the optimal treatment sequence challenging in clinical practice. The aim of this study was to evaluate the prostate-specific antigen (PSA) responses and overall survival (OS) among patients with mCRPC receiving
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Lu-PSMA-617 based on prior ARPI and taxane treatment exposure.
Methods:
This retrospective, observational study used real-world data from the PRECISION data platform, a harmonized dataset of advanced prostate cancer patients in the US from diverse clinical settings. Patients with mCRPC who had received ≥1 dose of
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Lu-PSMA-617 between March 23, 2022 and July 31, 2024, after prior treatment with ≥1 ARPI and ≥1 taxane, were included. To assess PSA response, the baseline PSA value obtained within 90 days before starting
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Lu-PSMA-617 was compared with the on-treatment PSA value obtained ≥28 days after
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Lu-PSMA-617 initiation. The number of patients achieving PSA reductions ≥50% (PSA50) and ≥80% (PSA80) were estimated, with patients classified into two cohorts based on prior ARPI and taxane exposure: (1) prompt cohort: after only 1 ARPI and 1 taxane, and (2) deferred cohort: >1 ARPI and/or >1 taxane. Patient characteristics and treatment patterns were evaluated descriptively. OS from
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Lu-PSMA-617 initiation was estimated using Kaplan–Meier methodology.
Results:
A total of 431 patients were included: 177 patients in the prompt cohort and 254 patients in the deferred cohort. Of patients in the deferred cohort, 185 (72.8%) received ≥1 ARPI and 1 taxane, 32 (12.6%) received 1 ARPI and ≥1 taxane, and 37 (14.6%) received ≥1 ARPI and ≥1 taxane. Median (interquartile range age was 73 (67–78) years and most demographic characteristics were balanced between groups. Patients in the deferred cohort had higher median PSA levels at baseline (63.1 ng/mL vs 25.2 ng/mL). PSA50 was observed in 18/33 (55%) patients in the prompt cohort vs 28/66 (42%) in the deferred cohort. PSA80 was observed in 13/33 (39%) patients in the prompt cohort vs 21/66 (31%) in the deferred cohort. Across both cohorts, median OS was 18.0 months (95% confidence interval [CI]: 15.1 months–not reached [NR]). Median OS was NR in patients in the prompt cohort vs 15.1 months in patients in the deferred cohort (95% CI: 11.6 months–NR).
Conclusions:
In this large real-world study, prompt initiation of
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Lu-PSMA-617 (after only 1 ARPI and 1 taxane) showed superior clinical outcomes versus deferred initiation of
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Lu-PSMA-617. Patients were more likely to achieve a PSA reduction ≥50% and ≥80% and had longer OS with prompt initiation of
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Lu-PSMA-617. These results may help to guide treatment sequencing in clinical practice.