(014) Current Trends in the Therapeutic Management of Metastatic Prostate Cancer in Clinical Practice

Background: While androgen deprivation therapy (ADT) remains the treatment backbone of metastatic prostate cancer (mPC), newer therapies like androgen receptor signaling inhibitors (ARSi) have become pivotal treatment options over recent years, in both the hormone-sensitive and the castration-resistant disease setting. In this evolving environment, it is important to better understand how patients with mPC are currently being treated in clinical practice and how the treatment landscape has changed over time. This can help to identify unmet medical needs and to develop new treatment strategies.

Objectives: We aimed to describe the treatment sequencing patterns and ARSi treatment duration for real-world patients with metastatic hormone sensitive and castration resistant prostate cancer (mHSPC, mCRPC).

Methods: This retrospective cohort study used the US-based nationwide Flatiron Health electronic health record-derived de-identified database. We included a broad cohort of patients with mPC who received at least one line of systemic therapy (≥2013) which must have started at least 90 days prior to administrative cutoff.
Sankey diagrams were used to describe treatment sequencing patterns for patients moving from mHSPC to mCRPC as well as for different lines of therapy within the mCRPC setting.
The Kaplan-Meier method was used to calculate real-world time to treatment discontinuation (rwTTD).

Results: Out of the 9,510 patients in the study cohort, 1,843 had information available in the mHSPC and mCRPC setting. Focusing on recent years (≥2018), about 52% of patients received either enzalutamide or abiraterone as first-line (1L) mCRPC therapy. While most of these patients had been treated with docetaxel or ADT monotherapy in mHSPC, a substantial fraction had already received an ARSi in the mHSPC setting. Out of the patients who received an ARSi in 1L mCRPC, many were treated with another ARSi in second-line (2L).
rwTTD was short for the second ARSi received, whether it was in 1L mCRPC (median=4.8 months [95% CI: 4.2-5.6]) or 2L mCRPC (median=6.0 months [5.5-6.4]).
Since their approvals in 2018 and 2019, abiraterone, enzalutamide and apalutamide have been used increasingly to treat mHSPC. In mCRPC, we observed a moderate decrease in the use of abiraterone and an increasing use of enzalutamide since its approval in this setting in 2012.

Conclusions: Our study showed an increasing use of ARSi in the management of patients with mPC over recent years. However, despite a limited benefit as suggested by the short rwTTD we observed, many patients received consecutive lines of ARSi therapies. This highlights the remaining high unmet need for novel therapies and further research to optimize treatment pathways.