From Genomic Testing to Olaparib Treatment: Real-World Utilization and Outcomes in BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

BACKGROUND: In November 2020, olaparib became the first approved poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) for metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 mutations (BRCAm) in the Netherlands. As randomized clinical trials include fitter patients, their findings may not fully reflect real-world outcomes. OBJECTIVE: The aim was to evaluate genomic testing practice and subsequent use and outcomes of olaparib monotherapy in a real-world BRCAm mCRPC population. METHODS: Data were derived from ten hospitals in the Dutch CAPRI-3 registry, including mCRPC patients diagnosed between 2016 and 2021. Those receiving olaparib in standard-of-care treatment after its national approval (from November 2020) were analyzed and grouped as taxane-naïve (TN) or post-taxane (PT). The primary endpoint was overall survival (OS). RESULTS: Among 1996 mCRPC patients, genomic analysis (somatic and/or germline) was performed in 23.4% (range 3.8-63.2% across hospitals), identifying BRCAm in 11.3% of patients. Tested patients differed significantly in age, comorbidities, and prior treatment. Among 35 eligible BRCAm patients, 27 (77.1%) received olaparib. TN patients (8/27) were significantly older and initiated olaparib at an earlier line of therapy. Median OS was 28.7 months (95% confidence interval (CI) not reached) in TN versus 10.5 months (95% CI 9.6-11.5) in PT patients (p = 0.003). Limitations include the retrospective design and small subgroups. CONCLUSIONS: Genomic testing application remained limited and uneven across centers. Most eligible patients received olaparib; TN patients seemed to benefit most.