Clinical outcomes associated with pathogenic genomic instability mutations in prostate cancer: a retrospective analysis of US pharmacy and medical claims data

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Background: Prostate cancer (PC) is a clinically heterogenous disease, and genetic mutations may be useful for patient risk stratification. This retrospective cohort study compared clinical outcomes, pharmacy use, and outpatient resource use in PC patients with and without pathogenic genomic instability mutations, including DNA repair deficiency (DRD) mutations and those in TP53, PTEN, and RB1.Methods: Patients ≥18 years newly-diagnosed with PC between June 2011–March 2016 were identified in medical and prescription claims databases linked to a genomic dataset. All-cause and PC-specific pharmacy use and outpatient resource use (office visits, laboratory tests, radiology examinations, and radiation therapies) over 1, 2, and 3 years and time to evidence of disease progression after PC diagnosis, based on secondary cancer diagnosis codes and treatments received, were evaluated in mutation carriers with ≥1 of 24 gene mutations and in a sub-set of DRD gene mutation carriers, with each compared to non-mutation carriers.Results: Mutation carriers (n = 274) and non-mutation carriers (n = 74) had similar demographic and clinical features. Non-mutation carriers had lower risks of developing metastasis and castration-resistant PC than mutation carriers (hazard ratio [HR] = 0.7, 95% CI = 0.5–0.9; HR = 0.5, 95% CI = 0.3–0.9, respectively) and DRD mutation carriers (HR = 0.5, 95% CI = 0.3–0.7; HR = 0.4, 95% CI = 0.2–0.7, respectively). Compared to non-mutation carriers, mutation carriers had more all-cause pharmacy claims over 2 years of follow-up (74.4 vs 59.1, p = 0.04) and more PC-specific pharmacy claims over 2 years (11.1 vs 6.5, p = 0.01) and 3 years (17.9 vs 9.8, p = 0.01) of follow-up. No differences were observed in outpatient resource use during the follow-up period by mutation status.Conclusion: PC patients carrying ≥1 pathogenic DNA instability mutation, and DRD mutation carriers specifically, had higher clinical burden than non-mutation carriers. Targeted therapies for these patients are needed to reduce clinical burden and associated healthcare resource utilization.

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