Compass Oncology, Portland, OR
Jay C. Andersen , Jagadeswara Rao Earla , Nicole Fulcher , Juliet Ndukum , Nicholas J. Robert , Mark E. Robson , Weiyan Li , Jamie Mejia
Background: Germline BRCA mutations (gBRCAm) are associated with a higher risk of breast cancer at a younger age. Generally, gBRCA gene testing is performed in patients perceived as high risk for gBRCAm. Olaparib, a targeted poly (ADP-ribose) polymerase inhibitor (PARPi), has significantly improved overall survival (OS) in the randomized, double-blind OlympiA trial of patients with HER2-negative gBRCAm and was subsequently approved for the adjuvant treatment of patients with gBRCAm HER2-negative high-risk early breast cancer (eBC) treated with neoadjuvant or adjuvant chemotherapy. This study examines the real-world patient characteristics, treatment patterns and OS by gBRCA status among patients with HER2-negative eBC in a US community oncology setting prior to olaparib US approval for treatment of eBC. Methods: This retrospective observational study used structured data from The US Oncology Network's iKnowMed database. Adult patients were included if diagnosed with HER2-negative eBC (stage I-III) and if they initiated systemic neoadjuvant or adjuvant therapy between January 1, 2012-December 31, 2018 (followed through December 31, 2021). Patients were excluded if they progressed to stage IV within 6 months after neoadjuvant treatment or were diagnosed with another primary cancer. Descriptive analyses assessed patient characteristics, early-stage systemic treatments and OS among patients by gBRCA status. Results: Among 19,258 patients with BC meeting initial criteria, 1436 (7.5%) had a documented gBRCA test result. Among them, 10% had gBRCAm (n = 141, 43% hormone receptor positive [HR+], 57% triple-negative BC [TNBC]), 90% BRCAwt (n = 1294, 70% HR+, 30% TNBC), and 1 had a variant of uncertain significance. Median age at surgery was numerically lower in gBRCAm (43 years) than gBRCAwt (48 years) patients. Treatments included neoadjuvant-only therapy (gBRCAm 58%; gBRCAwt 34%), adjuvant-only therapy (gBRCAm 42%; gBRCAwt 66%) and both neoadjuvant and adjuvant therapy (gBRCAwt 0.1%). Median OS in both study cohorts was not reached. Median follow-up from surgery was less than 4 years (gBRCAm 47 months; gBRCAwt 46 months). At 48 months, estimated survival was 95% in gBRCAm and 94% in gBRCAwt patients. Conclusions: In this cohort of patients with HER2-negative eBC, among the 7.5% with a documented gBRCA result, 10% were identified with gBRCAm, reinforcing the need for gBRCA testing. Using structured real-world data through 2021 (prior to PARPi approval for eBC) with limited follow-up of < 4 years, our study found that OS by gBRCA status was similar among patients with HER2-negative eBC. Our further research with chart review data containing granular clinical information looking at intermediate endpoints such as recurrence in eBC is under way.
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Abstract Disclosures
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