Hayes, Jennifer

e12502 Background: In March 2022, the United States Food and Drug Administration approved olaparib as adjuvant treatment (tx) for patients with germline BRCA1/2 pathogenic or likely pathogenic variants and HER2-negative eBC at high risk of recurrence who have been treated with neo-adjuvant or adjuvant chemotherapy. Approval was based on results from the OlympiA trial which demonstrated a significant increase in invasive-disease free survival [hazard ratio, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001] and overall survival [hazard ratio, 0.68; 99% CI, 0.47-0.97; P=0.009] with olaparib vs placebo. To date, there has been limited real-world data for eBC on olaparib utilization patterns and characteristics of olaparib users. Methods: This retrospective analysis using closed claims from KHM included adult pts with HER2-negative eBC receiving first olaparib prescription (index date) from March 11, 2022 to Nov 30, 2023. Continuous medical and pharmacy enrollment of ≥12 months pre-index and ≥30 days post-index was required. Pt characteristics were summarized descriptively, and Kaplan-Meier (KM) analysis was conducted for time-to-event utilization outcomes. Outcomes were evaluated for pts overall and stratified by hormone receptor (HR) status and race/ethnicity. Non-persistence was defined as minimum of 2 consecutive missed prescription fills. Medication possession ratio (MPR) was calculated as the sum of days of olaparib supply, divided by the total number of days from olaparib initiation to the last claim plus days of olaparib supply in the last claim. Results: We identified 176 pts with HER2-negative eBC who received olaparib. Median age was 44 years, and the majority (66.5%) had commercial insurance. KM-calculated median persistence on olaparib was 11 months (95% CI: 9.2-12.2); overall, adherence measured by MPR ≥80% was 74.2% by month 6 of olaparib use; adherence is higher among Caucasian than non-Caucasian pts (Table). While the majority of HR+/HER2- pts (77.9%, N=53/68) took olaparib concurrently with other (88.7% hormonal) adjuvant tx, most TNBC pts (70.4%, N=76/108) received olaparib alone. Among TNBC pts who took olaparib concurrently with other adjuvant tx (N=32/108), 81.3% received olaparib combined with immunotherapy. Conclusions: Our study provides evidence of favorable persistence and adherence to adjuvant olaparib in a real-world setting and data on utilization of olaparib concurrently with other tx. Recent approvals of other adjuvant tx for HER2- high-risk eBC warrants further research on the efficacy of olaparib used alone, versus olaparib combined or sequenced with other treatments. Olaparib MPR ≥80% by follow-up time points between Caucasians and non-Caucasians. Cohorts 30 days 60 days 180 days 365 days Caucasians (N=70) 92.5% 71.7% 80.6% 90.9% Non-Caucasians(N=55) 88.7% 66.7% 70.0% 50.0%

1113 Background: Testing for BRCA1/BRCA2 mutations (BRCAm) aids systemic treatment decisions for patients (pts) with metastatic breast cancer (mBC). This retrospective study explored real-world germline/tumor (g/t) BRCA testing patterns and PARP inhibitor (PARPi) use in US pts with mBC. Methods: Data from pts ≥18 years old diagnosed with HER2-negative mBC from 2014–2022 were captured in the nationwide Flatiron Health electronic health record-derived deidentified database. Patterns and timing of prospective or incidental BRCA testing were compared across mBC subtypes (hormone receptor-positive [HR+ mBC]/triple-negative mBC [mTNBC]) and disease stage (recurrent/ de novo). BRCAm prevalence was compared by testing modality and mBC subtype. PARPi initiation was assessed in pts with mBC diagnosed from 2018 onwards and a positive BRCAm test result. Clinical characteristics were compared by receipt of a BRCA test, testing modality, and PARPi initiation. Real-world overall survival (OS) by PARPi use was estimated using the Kaplan-Meier method. Results: Of 15,006 pts (including 12,349 with HR+ mBC; 1998 with mTNBC), 8178 (54.5%) did not receive any type of BRCA test, 4654 (31.0%) received a gBRCA test, 3075 (20.5%) received a tumor tissue DNA (ttDNA) test, and 1418 (9.4%) received a circulating tumor DNA (ctDNA) test. BRCA testing prevalence was numerically higher in pts with mTNBC (n=1164; 58.3%) than in pts with HR+ mBC (n=5323; 43.1%). As expected, testing prevalence was higher with ttDNA than with ctDNA (mTNBC: n=569 [28.5%] vs n=137 [6.9%]; HR+ mBC: n=2339 [18.9%] vs n=1224 [9.9%]). Over 93% of pts (recurrent and de novo) who received a tBRCA test were tested after an mBC diagnosis, and >1/3 were tested after first-line therapy, with median times from diagnosis to a ttDNA and ctDNA test of 127 and 431 days, respectively. Both gBRCA and tBRCA testing rates increased from 2014–2022, and testing occurred earlier in pts with recurrent than de novo disease. Among pts with tBRCAm, 66.0% had HR+ mBC, and 25.6% had mTNBC. BRCA1 mutations were more common in mTNBC (59.0%) than in HR+ mBC (22.9%) tumors. Of 219 pts with tBRCAm tumors who were diagnosed with mBC from 2018 onwards, PARPi was initiated in 39/74 (52.7%) pts with gBRCAm, 15/71 (21.1%) pts who were gBRCAm-negative, and 19/74 (25.7%) pts with gBRCAm status unknown. Among pts with g or tBRCAm and available OS data, median OS was numerically longer in pts who received PARPi (32.3 months [95% CI: 24.2, 47.4], n=128) versus pts who did not (29.0 months [95% CI: 21.9, 31.9], n=204; median follow-up time 23.2 months). Conclusions: While NCCN guidelines recommend gBRCA testing for all pts with mBC, more than half of pts with HER2-negative mBC (56.9% of pts with HR+ mBC) did not receive any BRCA test. Among pts with tBRCAm, ~2/3 had HR+ disease. Despite the potential benefits of PARPi for pts with BRCAm mBC, utilization remained low from 2018–2022.