Abstract PS10-53: Treatment Patterns and Clinical Outcomes Among Patients with germline BRCA1/2 mutated (gBRCA1/2mut) HER2+ Advanced Breast Cancer (ABC): Results from a US Real-world Study
Authors: Obeid Elias , Parikh Rohan C , Esterberg Elizabeth , Arondekar Bhakti , Hitchens Abigail , Arruda Lillian Shahied , Niyazov Alexander 
Published: February 2021

Background: gBRCA1/2mut ABC represents ~5% of all breast cancer (BC), although a fair estimate of gBRCA1/2mut HER2+ BC remains to be determined. HER2-targeted therapy is the current standard of care for these patients with HER2+ BC. While PARP inhibitors (PARPi) are approved for the treatment of gBRCA1/2mut HER2- ABC, recently, NCCN updated its guidelines (v6.2020) to additionally consider the use of PARPi in patients with gBRCA1/2mut HER2+ metastatic BC. However, clinical trials have not evaluated the efficacy of PARPi among patients with gBRCA1/2mut HER2+ metastatic BC. In order to establish a baseline reference point, we assessed real-world treatment patterns and clinical outcomes among patients with gBRCA1/2mut HER2+ ABC.

Methods: US Oncologists retrospectively reviewed charts (July 2019-June 2020) of randomly selected patients ≥18 y, with gBRCA1/2mut ABC who received ≥1 cytotoxic chemotherapy (CT) regimen(s) for ABC between Jan 2013-April 2018. A descriptive analysis was performed for the HER2+ patients including 1st line ABC treatment patterns. Clinical outcomes (1st line ABC PFS rates) were estimated using the Kaplan-Meier method. PARPi clinical outcomes data were immature given its recent launch. Additional analyses evaluating outcomes in patients receiving PARPi are planned.

Results: Of the 387 patients with gBRCA1/2mut ABC included in the study, 82 (21%) female patients had HER2+ disease. Of the gBRCA1/2mut HER2+ patients, median age was 56y, 72% were white. Clinical characteristics: 62% HR+/HER2+, 37% HR-/HER2+, and 1% had unknown HR/HER2+ ABC. Treatments in the 1st line setting for HR+/HER2+ ABC patients (n=51) included CT (55%) and CT + HER2-targeted therapy (43%). First-line treatments used for HR-/HER2+ ABC patients (n=30) included CT + HER2-targeted therapy (77%) and CT (20%). 12-month PFS rate for 1st line HR+/HER2+ patients was 77% and for HR-/HER2+ patients was 64%. Later line treatments will be presented.

Conclusion: In this analysis of HER2+ patients with gBRCA1/2mut ABC, unexpectedly low rates of HER2-targeted therapy were observed in patients with HR+/HER2+ disease. Appropriately high rates of HER2-targeted therapy with CT was observed among gBRCA1/2mut HR-/HER2+ patients. Treatment patterns among patients with non-gBRCA1/2mut HER2+ ABC in a real-world setting need to be evaluated. Clinical outcome findings from this study demonstrate the need to better understand best treatment strategies for this patient population. As PARPi are not yet approved for patients with gBRCA1/2mut HER2+ ABC, studies assessing efficacy of PARPi +/- HER2-targeted therapy are warranted.

Funding: Pfizer

Citation Format: Elias Obeid, Rohan C Parikh, Elizabeth Esterberg, Bhakti Arondekar, Abigail Hitchens, Lillian Shahied Arruda, Alexander Niyazov. Treatment Patterns and Clinical Outcomes Among Patients with germline BRCA1/2 mutated (gBRCA1/2mut) HER2+ Advanced Breast Cancer (ABC): Results from a US Real-world Study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-53.