Abstract

Abstract Background Historically, the standard-of-care treatments for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC) have included targeted therapies, such as trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1), which have shown efficacy in clinical trials. Treatment choice and sequencing for patients with HER2+ mBC after first-line therapy have not been well delineated in the US real-world setting. Methods Patients who received at least two lines of therapy for HER2+ mBC diagnosed from January 2013 - April 2019 were selected from the Flatiron Health electronic health record-derived database. The Flatiron database is nationwide and comprises deidentified patient-level structured and unstructured data curated via technology-enabled abstraction in the US. The index date was the start date of the second line of therapy (2L). Treatment patterns from 2L onward were examined. Baseline information included disease stage at diagnosis and prior treatment for mBC. Duration of therapy was estimated using the Kaplan-Meier method. Results Among the 1390 patients with HER2+ mBC with a documented 2L therapy, the mean age at the initiation of 2L therapy was 60.4 years. Patients had one (n = 514; 37.0%), two (n = 390; 28.1%), or three or more (n = 461; 33.2%) metastatic sites by the start of 2L therapy. The most common metastatic sites were bone (n = 872; 62.7%), lung (n = 494; 35.5%), liver (n = 473; 34.0%), and brain (n = 223; 16.0%). The majority of patients (n = 1141; 82.1%) had positive hormone receptor status. Nearly half of patients (n = 601; 43.2%) had stage IV disease at their initial breast cancer diagnosis, 289 (20.8%) had stage III, and 277 (19.9%) had stage II. Before 2L therapy, 720 patients (51.8%) received a HER2-targeted combination therapy, 337 (24.2%) received hormone therapy alone, and 209 (15.0%) received HER2-targeted monotherapy. Among all included patients, 481 (34.6%) had two lines of systemic therapy for mBC, 359 (25.8%) had three, and 550 (39.6%) had four or more. Of these patients, 1290 (92.8%) had used a HER2-targeted agent (monotherapy or in combination) in at least one line of therapy, and 1108 (79.7%) had two or more lines of therapy containing a HER2-targeted agent. In 2L, the most frequently prescribed regimens were pertuzumab + trastuzumab + taxane (n = 246; 17.7%), T-DM1 monotherapy (n = 213; 15.3%), and trastuzumab monotherapy (n = 192; 13.8%). Overall, in 2L, 721 (51.9%) of all included patients received HER2-targeted combination therapy, 427 (30.7%) received HER2-targeted monotherapy, 82 (5.9%) received chemotherapy, and 118 (8.5%) received hormone therapy alone. Hormone therapy was combined with chemotherapy or targeted therapy in 622 patients (44.7%). Median (95% CI) duration of 2L therapy was 6 (6-6) months. Among the 909 patients who had third-line (3L) therapy, the most common regimens were T-DM1 (n = 170; 18.7%), pertuzumab + trastuzumab + taxane (n = 77; 8.5%), and hormone therapy alone (n = 59; 6.5%). Overall, in 3L, 446 patients (49.1%) had HER2-targeted combination therapy, 283 (31.1%) had HER2-targeted monotherapy, and 78 (8.6%) had chemotherapy, with hormone therapy added to chemotherapy or targeted therapy in 388 patients (42.7%). Median (95% CI) duration of 3L therapy was 5 (4-6) months. Conclusions The results of this real-world study of patients receiving care in community-based oncology clinics suggest that treatment patterns in later-line settings are variable, with no clear treatment approach for this patient population and patients often being re-treated with the same HER2-targeted therapies. As additional targeted therapies have recently been approved for HER2+ mBC with improvements in patient outcomes, future examination of the treatment landscape is warranted. Citation Format: Jenna Collins, Beth Nordstrom, Jackie Kwong, Brian Murphy, Melissa Pavilack. A real-world evidence study of treatment patterns among patients with HER2-positive metastatic breast cancer [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 PS7-82.

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