Evaluation of drug-drug interactions and progression-free survival in patients with prostate cancer treated with androgen receptor pathway inhibitors using the Drug-PIN software: The DDI-AID, a real-world observational study from the Meet-URO Network.

Abstract

e17019 Background: Androgen Receptor Pathway Inhibitors (ARPIs) are commonly used in metastatic prostate cancer (mPC). Given the advanced age and comorbidity burden typical of this population, polypharmacy is frequent in mPC patients, increasing the risk of clinically relevant drug–drug interactions (DDIs), which are rarely assessed in routine practice. The Drug-PIN software, an intelligent system analyzing phenotypic data and DDIs, has been shown to identify patients at risk of severe toxicity or reduced survival. The DDI-AID study investigates the association of DDIs with survival in patients with mPC treated with ARPI in a real-world setting. Methods: DDI-AID is an Italian, multicenter, retro-prospective observational study. The study included 245 consecutive patients with mHSPC or mCRPC treated with ARPI, and receiving at least one concomitant medication. Clinically relevant DDIs were assessed at ARPI initiation and patients were classified into no / low- or high-risk-DDIs groups. Progression-free Survival (PFS) was defined as time from ARPI start to disease progression or death. Survival analyses were performed using Kaplan-Meier and Cox proportional hazards models were adjusted for relevant clinical covariates. The study was approved by Ethical Committee Lazio Area 1 (Ref. n. 7364, 2023/11/08). Results: At the data cut-off (15 January 2026), a total of 245 patients were included. The median age was 74 years (range 52–94), and the median Charlson Comorbidity Index (CCI) was 3 (range 1-8). Polypharmacy was observed in 116 patients (47%), and high-risk DDIs were identified in 80 patients (33%). Regarding treatments, 68 (28%) patients received Abiraterone, 97 (39%) Enzalutamide, 71 (29%) Apalutamide and 9 (4%) Darolutamide with Docetaxel. A total of 138 (56%) patients received ARPI in the mHSPC setting and no significant differences were observed in the ADT received (p = 0,093). The median PFS was 35.9 months (95% CI 27.8-NR) in the low-risk-DDI group compared to 19.8 months (95% CI 15.1-NR) in the high-risk DDI group. In the multivariable analysis, adjusted for age (≤74 vs ≥75 years), performance status (0 vs 1–3), Charlson Comorbidity Index (0–1 vs ≥2), and presence of visceral metastases, the presence of low-risk DDIs remained significantly associated with longer PFS (HR 0.59, 95% CI 0.38–0.90, p = 0.016). Moreover, treatment with ARPIs in the mHSPC setting (HR 0.49, 95% CI 0.31–0.78, p = 0.003) and achieving a PSA nadir ≤2 ng/mL (HR 0.16, 95% CI 0.09–0.26, p < 0.001) were independently associated with longer PFS. Conclusions: In this real-world cohort, DDIs are common in patients treated with ARPIs and the presence of high-risk DDIs was associated with reduced PFS. These findings highlight the importance of medication review in routine clinical practice.