Prevalence and prognosis of BRCAm, homologous recombination repair mutation (HRRm) or HR deficiency positive (HRD plus ) across tumor types.

e18802 Background: BRCAm, HRRm, or HRD+ may be predictive of response to poly (ADP-ribose) polymerase inhibitors (PARPi) with/without immunotherapy (IO). However, there is limited data on the prevalence of these biomarkers and their impact on overall survival (OS) among patients who are not treated with PARPi or IO. Methods: This is a retrospective observational study across 15 available tumor types, using data from the de-identified Flatiron Health - Foundation Medicine (FMI) clinicogenomic database collected up to Dec 31, 2020. The de-identified data originated from ̃280 US cancer clinics (̃800 sites of care). Eligible patients were aged ≥ 18 years, diagnosed with advanced/metastatic solid tumors in 2018-2019. BRCAm, HRRm, and HRD were assessed by FMI F1CDx. HRD+ was defined as genomic loss of heterozygosity (gLOH) ≥16. OS analysis from second line therapy initiation (2L, primary index date) was performed as primary analysis since this population had high unmet medical need, and most patients were sequenced after 1L. Patients were excluded if PARPi/IO started on the index date or earlier or if patients died before the index date; and patients were censored as of PARPi/IO initiation if PARPi/IO was started later than the index date. OS was analyzed using the Kaplan-Meier method and Cox proportional hazards model, adjusted for age, sex, and tumor type. Results: A total of 9,462 patients with advanced/metastatic solid tumors were included, with 52% women and mean age of 66 years. The top five tumor types represented more than 75% of the patients, including non-small cell lung cancer (27%), colorectal (19%), breast (13%), pancreatic (8%) and gastric (8%) cancers. Known or suspected deleterious BRCAm was observed in 4.6% of patients across tumors and varied by tumor type, with the highest prevalence in ovarian cancer (13.0%). Total HRRm prevalence was 13.2% across tumor types with prostate cancer (25.9%) as the highest, and the prevalence of HRD+ was 20.6% cross tumor types with breast cancer (34.4%) as the highest. The adjusted hazard ratio (aHR) for OS from initiation of 2L therapy for patients with BRCAm vs BRCA wild type (BRCAwt) was 0.81 (95%CI, 0.61-1.07). Comparable results were observed when calculating OS from 1L or 3L therapy. The aHR of OS from 2L therapy with HRRm vs HRRwt was 0.92 (0.78-1.09) and 1.20 (1.01-1.43) for patients with HRD+ vs HRD negative (HRD-). Conclusions: The prevalence of BRCAm, HRRm, and HRD+ varies widely by tumor type. There was no association between BRCA/HRRm status and OS, yet HRD+ might be associated with shorter OS among patients who were not treated with PARPi or IO across the evaluated tumor types.[Table: see text]