Patterns of next-generation sequencing and associated next-line systemic therapy use in metastatic prostate cancer.

Abstract

105 Background: Next-generation sequencing (NGS) testing is used for prognostication and to guide treatment choice in metastatic prostate cancer (mPC). While NGS testing is increasingly available, how its usage has impacted real-world selection of next line therapies including olaparib in mPC is unclear. Methods: We performed a retrospective observational study using the real-world nationwide U.S. Flatiron Health electronic health record-derived de-identified mPC database with patients diagnosed between January 1 st , 2013, and July 30 th , 2024. Due to limitations of follow-up, patients diagnosed with mPC in 2024 were excluded. Rates of patients with documented NGS testing within 6 months of metastatic prostate cancer diagnosis, short-interval changes in systemic therapy defined as initiation of a new therapy within 30 days after NGS testing, and olaparib initiation within 60 days of NGS testing were analysed. Results: A total of 24,222 mPC patients were included, of which 6282 (25.94%)had at least 1 documented NGS test and 1494 (23.78%) of those patients had more than 1 NGS test. NGS test documentation after metastatic diagnosis increased from 0.175% in 2013 to 22.8% in 2023. The median time from metastatic diagnosis to initial NGS testing was 413 days (IQR 76-993). The percentage of NGS tests associated with short-interval initiation of a new line of therapy increased from 14.29% of patients receiving NGS testing in 2014 to 24.19% of patients receiving NGS testing in 2023. The most common therapies initiated within 30 days after NGS testing were abiraterone (37.75%), enzalutamide (13.91%), and docetaxel (10.93%). Among patients with documented NGS testing, the percent who initiated olaparib within 60 days of an NGS test increased from 0.31% in 2015 to 17.34% in 2024, with the greatest year-on-year increase in 2020 corresponding to FDA approval for patients with homologous recombination repair gene alterations. Median time to olaparib initiation after metastatic diagnosis was 798 days (IQR 455-1383). Conclusions: There was a significant increase in rates of documented NGS test for patients diagnosed with mPC over the past decade. Furthermore, systemic therapy change appears to be more frequently influenced by NGS testing, with a significant increase in associated olaparib initiation as next-line therapy.