Real-world first-line systemic therapy patterns in metastatic castration-resistant prostate cancer

Introduction: Several systemic therapies have demonstrated a survival advantage in metastatic castration resistant prostate cancer (mCRPC). Access to these medications varies significantly worldwide. In Australia until recently, patients must have received docetaxel first, unless unsuitable for chemotherapy, despite no evidence suggesting superiority over androgen receptor signalling inhibitors (ARSIs). Our study investigated real-world systemic treatment patterns in Australian patients with mCRPC. Methods: The electronic CRPC Australian Database (ePAD) was interrogated to identify mCRPC patients. Clinicopathological features, treatment and outcome data, stratified by first-line systemic therapies, were extracted. Comparisons between groups utilised Kruskal-Wallis tests and Chi-Square analyses. Time-to-event data were calculated using Kaplan-Meier methods and groups compared using log-rank tests. Factors influencing overall survival (OS) and time to treatment failure (TTF) were analysed through Cox proportional hazards regression models. Results: We identified 578 patients who received first-line systemic therapy for mCRPC. Enzalutamide (ENZ) was most commonly prescribed (n=240, 41%), followed by docetaxel (DOC, n=164, 28%) and abiraterone (AA, n=100, 17%). Patients receiving ENZ or AA were older (79, 78.5years respectively) compared with DOC (71years, p=0.001) and less likely to have ECOG performance status 0 (45%, 44%, 59% in ENZ, AA and DOC groups respectively p<0.0001). Median TTF was significantly higher in those receiving ENZ (12.4months) and AA (11.9months) compared to DOC (8.3months, p<0.001). PSA50 response rates and OS were not statistically different. Time to developing CRPC>12months was independently associated with longer TTF (HR 0.67, p<0.001) and OS (HR 0.49, p=0.002). Conclusion: In our real-world population, ENZ and AA were common first-line systemic therapy choices, particularly among older patients and those with poorer performance status. Patients receiving ENZ and AA demonstrated superior TTF compared to DOC, while OS was not statistically different. Our findings highlight the important role of ARSIs, given the variability of access worldwide.