Enzalutamide Plus ADT for the Treatment of mHSPC: Real-World Evidence from a Bulgarian Cohort.

Background/

Objectives

The pivotal ARCHES trial demonstrated the clinical benefit of the second-generation androgen receptor signaling inhibitor enzalutamide in combination with androgen deprivation therapy (ADT) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). However, real-world evidence on the efficacy of enzalutamide plus ADT in mHSPC remains very limited. The current work provides real-world data on the efficacy of this combination in a Bulgarian cohort of patients with mHSPC.

Methods

Patients treated with enzalutamide plus ADT across 48 hospitals between 1 January 2022 and 31 December 2025 were included in our retrospective analysis. Data were extracted from electronic health records, for which large language model (LLM) algorithms were employed, utilizing the Danny Platform (Sqilline Health, Sofia, Bulgaria). Treatment outcome was evaluated based on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). Iterative proportional fitting was performed to improve comparability between the real-world and trial populations by accounting for differences in baseline characteristics.

Results

Baseline characteristics were largely comparable among the ARCHES and our real-world cohort, with the most notable differences observed in prior systemic treatment exposure. A considerably higher ORR was reported for ARCHES (85.9%) in contrast to our cohort descriptive ORR (12.3%) derived from physician EHR notes, likely reflecting routine clinical documentation practices, whereas CBR values were comparable (89.6% in our cohort versus 95.9% in ARCHES). While median values were not calculable, estimated PFS and OS were consistent with those in ARCHES.

Conclusions

Real-world outcomes from our Bulgarian cohort of patients with mHSPC are largely consistent with those observed among enzalutamide-treated participants in the ARCHES trial.