Trends in estimated PARP inhibitor eligibility and benefit among US epithelial ovarian cancer patients

To estimate the annual percentage of patients with epithelial ovarian cancer (EOC) who could be eligible for and benefit from PARP inhibitor therapy amidst changing US Food and Drug Administration (FDA)-approved indications. This is a simulated retrospective observational study using publicly available data on patients with advanced-stage EOC. PARPi eligibility is based on FDA approvals and withdrawals from 2014 through 2023, along with published demographic and genomic data. Clinical trial data is used to estimate treatment benefit. PARPi including olaparib, niraparib, and rucaparib are analyzed in aggregate with sub-analyses by molecular classification and treatment timing. Results are reported as the percentage of EOC patients appropriate for any cancer-directed therapy. PARPi were approved for 9 different indications in EOC between 2014 and 2021; reduced to 6 indications by 2023. Eligibility increased from 2.0% (95% CI,1.3%–1.6%) in 2014 to a maximum of 93.4% (95% CI,90.1%–94.6%) in 2021. The maximum percentage of patients with 2-year PFS benefit was 22.0% (95% CI, 17.2%–26.8%) in 2021, projected to decrease to 13.0% (95% CI, 9.9%–15.9%) in 2024. Most of this decrease was seen in the homologous recombination deficient, BRCA wild-type population (8.4% to 4.0%). PARPi eligibility increased at a greater rate than benefit resulting in a low population-level benefit-to-eligibility ratio until 2021. Recent FDA withdrawals improved this ratio with an accompanied decrease in the absolute number of patients benefiting. To further optimize population-level benefit-to-eligibility ratio of targeted therapies in ovarian cancer, we need to identify better biomarkers, treatment combinations, and novel therapeutic targets. [Display omitted] •PARP inhibitor eligibility in ovarian cancer increased at a greater rate than benefit until 2021.•The greatest difference between eligibility and benefit is seen in the homologous recombination proficient population.•By our estimates, ovarian cancer PARP inhibitor benefit increased to 22% by 2021− projected to decrease to 13% in 2024.•To further increase benefit from targeted therapies we need to identify better biomarkers and novel therapeutic targets.