Outcomes for
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Lu-PSMA-617 with and without concurrent use of ARPIs in patients with mCRPC.
Authors: Muniz Miguel , Sartor Alton Oliver , Orme Jacob , Koch Regina , Quevedo Fernando , Kase Adam McLain , Riaz Irbaz Bin , Naqvi Syed Arsalan Ahmed , Andrews Jack , Thorpe Matthew , Kendi Ayse T. , Bilgin Gokce Belge , Johnson Geoffrey , Kwon Eugene D. , Childs Daniel S 
Published: February 2025

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Background:
We now have more than a decade of experience using Androgen Receptor Pathway Inhibitors (ARPIs) across various disease states of prostate cancer, and the safety of their combination with Lutetium-177–PSMA-617 has been demonstrated in VISION and other large randomized clinical trials. However, real-world data on treatment patterns and outcomes involving combination therapies with
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Lu-PSMA-617 remain limited.
Methods:
For this analysis, we utilized the Mayo Clinic Rochester radiopharmaceutical database, a prospectively maintained retrospective database containing all patients who received
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Lu-PSMA-617 at our institution. We focused on patients who started treatment from March 2022 to March 2023. Patients receiving an ARPI (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) during the course of
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Lu-PSMA-617 treatment were identified, inclusive of patients who continued using an ARPI prescribed as a prior line of treatment and those who started (i.e., switched) to a new ARPI. Baseline clinicopathologic and imaging characteristics were abstracted and compared using the Mann-Whitney U and Chi-square tests. Best PSA response during treatment was reported as a percent decline from baseline. Survival was calculated from the date of the first cycle of
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Lu-PSMA-617. PSA50 response and overall survival (OS) outcomes for the two groups (concurrent use of ARPI vs.
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Lu-PSMA-617 alone) were compared using the Chi-square test and Kaplan-Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors.
Results:
An ARPI was prescribed to 106 of the 256 patients (41.4%) starting
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Lu-PSMA-617 in the interval of March 2022 to March 2023. With regards to baseline characteristics, those receiving an ARPI concurrently with
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Lu-PSMA-617 had a lower PSA (3.4 vs 29.7 ng/mL, p < 0.001) and a lower frequency of bone (77.4% vs. 87.4%, p = 0.035) and visceral metastases (18.9 vs 34%, p = 0.008) at start of treatment. Median follow-up for the overall cohort (IQR) was 19.1 months (8.7 – 23.6). Patients receiving an ARPI plus
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Lu-PSMA-617, as compared to
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Lu-PSMA-617 alone, were more likely to complete all 6 planned doses of treatment (63.2% vs. 48.7%, p < 0.001), though the PSA50 response rate was similar (49.1% vs 47.3%, p = 0.786). Median OS [95% CI] for the overall cohort was 21.3 [16.7 – 25.9] months and significantly longer for those receiving ARPI with
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Lu-PSMA-617 (NR [NE – NE]) as compared to
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Lu-PSMA-617 alone (15.3 mo [11.6 – 19.1], p < 0.001). However, on multivariate analysis including known prognostic variables, use of ARPI was not independently associated with improved survival (HR = 1.03 [CI: 0.68 to 1.55], p = 0.891).
Conclusions:
Patients receiving an ARPI with
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Lu-PSMA-617 were more likely to complete all 6 cycles of treatment, but no clear differences in survival were observed on multivariate analysis.