225Ac-PSMA / 177Lu-PSMA Tandem Therapy for Metastatic Castration-Resistant Prostate Cancer – A Prospective Phase 3 Randomized Study from Azerbaijan

Introduction: Our study presents preliminary findings from a phase 3, single-center, prospective, randomized, two-arm controlled study.

Methods: Patients with advanced-stage mCRPC, resistant to ADT (e.g., enzalutamide or abiraterone acetate), were randomized to receive a combination of 225-Actinium / 177- Lutetium labeled PSMA (PSMA tandem treatment) or the current standard-of-care with docetaxel. Control visits were conducted to evaluate PFS and OS in both arms. Serial prostate-specific antigen (PSA) measurements were obtained for response assessment. Hematological and non-hematological adverse effects were recorded.

The study was conducted according to the protocol approved by the institutional committee on ethics in human investigation, following the principles of the Declaration of Helsinki of the World Medical Association.

Results: A total of 93 patients were included in the study (table1). In the PSMA arm (PA), 110 cycles (median 2; range 1-6) were administered, while the Standard arm (SA) received 73 cycles (median of 2 cycles (range 1-10).

In the PA, no severe hematologic toxicity or nephrotoxicity was noted; the commonest toxicity reported was grade I-II xerostomia, observed in 36% of patients. In the SA, treatment discontinuation due to toxicities affected less than 10% of patients.

Conclusions: We established, for the first time through randomization, the benefit of PSMA radiolabeled tandem therapy in mCRPC patients. Combining alpha (225Ac) and beta (177Lu) radionuclides minimized adverse effects, while preserving treatment efficacy. PSMA radiolabeled therapy opens doors to a brighter future for patients, promising to significantly extend the boundaries of disease progression delay.

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