225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience
Khreish F, Ebert N, Ries M, Maus S, Rosar F, Bohnenberger H, Stemler T, Saar M, Bartholomä M, Ezziddin S (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 47
Pages Range: 721-728
Journal Issue: 3
DOI: 10.1007/s00259-019-04612-0
Abstract
Purpose: Up to 30% of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) never respond or develop resistance to 177Lu-labeled PSMA-targeted radioligand monotherapy. Single-agent PSMA-targeted radioligand therapy (PRLT) with the alpha-emitter 225Ac showed promise against mCRPC but may cause severe and/or persistent xerostomia, which may substantially impair patients’ quality-of-life. We hypothesized that when 177Lu-PSMA ligand alone is ineffective, tandem therapy with low-activity 225Ac-PSMA ligand plus full activity of the beta emitter may enhance efficacy while minimizing xerostomia severity. Methods: We retrospectively analyzed pilot experience with 1 course of 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy in our first 20 patients with mCRPC receiving this intervention after insufficiently responding to 177Lu-PSMA-617 monotherapy. This cohort had late-stage/end-stage disease with high baseline prostate-specific antigen (PSA) concentration (median 215 ng/mL), heavy pre-treatment (abiraterone and/or enzalutamide, and 177Lu-PRLT [median cumulative activity, 26.3 GBq] in 20/20 patients, 100%; docetaxel and/or cabazitaxel in 13/20 patients, 65%), and frequent Eastern Cooperative Oncology Group performance status of 2 (8/20 patients, 40%). Results: Median (minimum–maximum) administered activities were 225Ac-PSMA-617, 5.3 (1.5–7.9) MBq, and 177Lu-PSMA-617, 6.9 (5.0–11.6) GBq. Significant responders to tandem therapy received 177Lu-PSMA-617 monotherapy as maintenance (median [minimum–maximum]: 1 [0–5] cycle). After a median (minimum–maximum) 22 (14–63) weeks’ follow-up, 13/20 patients (65%) had as best biochemical response a PSA decline > 50%. Median (95% confidence interval) progression-free survival was 19 (12–26) weeks, and overall survival was 48 (4–92) weeks post-tandem therapy administration. Xerostomia was reported as grade 1 (very mild) in 8/20 patients (40%), grade 2 (mild) in 5/20 (25%), and grade 3/4 in 0/20. Conclusions: Our results suggest that a single course of tandem therapy with low-activity 225Ac-PSMA-617/full-activity 177Lu-PSMA-617 may safely enhance response to PRLT in men with late-stage/end-stage mCRPC while minimizing xerostomia severity. Formal study of this combination is warranted.
Involved external institutions
Germany (DE)How to cite
APA:
Khreish, F., Ebert, N., Ries, M., Maus, S., Rosar, F., Bohnenberger, H.,... Ezziddin, S. (2020). 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. European Journal of Nuclear Medicine and Molecular Imaging, 47(3), 721-728. https://doi.org/10.1007/s00259-019-04612-0
MLA:
Khreish, Fadi, et al. "225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience." European Journal of Nuclear Medicine and Molecular Imaging 47.3 (2020): 721-728.
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