Real-World Results of Olaparib for HRRm+ Castration-Resistant Prostate Cancer

A recent real-world analysis provides data on treatment patterns, biomarker testing, and clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair gene mutations (HRRm) treated with olaparib monotherapy. The study draws on data from the ConcertAI Oncology Dataset and sheds light on the impact of treatment timing and prior therapy on key outcomes.

Olaparib, a PARP inhibitor, has been shown in clinical trials to extend progression-free survival (PFS) for patients with HRRm+ mCRPC compared to standard treatments, such as enzalutamide or abiraterone. This retrospective study evaluated 144 patients diagnosed between 2012 and 2023 who received olaparib following prior exposure to novel hormonal agents (NHAs). The analysis included patients with germline or somatic mutations in key HRR genes, including BRCA1, BRCA2, ATM, and others.

The results showed that 41% of patients initiated olaparib within the first three lines of therapy (≤3L), while 59% received it as a fourth-line or later treatment (4L+). The study highlighted a longer median real-world time on treatment (rwToT), real-world PFS (rwPFS), and real-world overall survival (rwOS) among patients treated with olaparib earlier (2L or 3L) compared to later (4L+). Furthermore, patients who avoided chemotherapy prior to olaparib initiation exhibited better outcomes than those who had received chemotherapy.

A significant finding was the timing of biomarker testing. Patients receiving olaparib in 4L+ had longer intervals between initial biomarker testing and therapy initiation, potentially delaying access to the benefits of targeted treatment. Somatic testing was more frequently employed in later-line settings, suggesting a gap in early identification of actionable mutations. The data reinforce the importance of early and comprehensive biomarker testing to guide timely initiation of targeted therapy.

This study underscores the value of olaparib as an effective option for HRRm+ mCRPC and highlights the need for proactive biomarker testing to optimize treatment outcomes.