Abstract

Abstract Background Historically, standard-of-care treatments for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC) have been pertuzumab and trastuzumab combined with a chemotherapeutic agent in first line (1L), and trastuzumab emtansine (T-DM1) in the second line (2L). However, two new treatments have recently been approved for patients who previously received HER2-targeted therapy; fam-trastuzumab deruxtecan-nxki [Enhertu®] and tucatinib [Tukysa] (in triplet combination) in 2019 and 2020, respectively. The goal of this study was to characterize treatment patterns of patients with HER2+ mBC from receipt of first line therapy and subsequent treatments received in real world community oncology practices. Methods Adults diagnosed with HER2+ mBC from January 2013 – January 2021 were selected from the Flatiron Health electronic health record–derived database; a US-wide database curated from community clinics that comprises de-identified patient-level structured and unstructured data. Patients were followed from index date (start of 1L therapy) to death or last activity date. Descriptive statistics reported baseline patient characteristics and treatment patterns. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and real-world overall survival (rwOS) were estimated using the Kaplan-Meier method. Results A total of 2,074 mBC HER2+ patients with at least 1 line of therapy were included during the study time period. Median follow-up time was 26.0 months (Interquartile range [IQR]: 12.6-44.7). Patients were mostly white (62.7%), median age 61 years (IQR:24-84), 43.0% were stage IV at initial breast cancer diagnosis, and 62.8% had positive hormone receptor (HR) status. Of the 2,074 patients in our study population, 1,159 (55.8%) received 2L therapy, and 584 (28.2%) received a 3L therapy. In terms of 1L therapy, 1,607 (77.5%) received a trastuzumab-based (T-based) regimen, 205 (9.9%) received chemotherapy only, and 153 (7.4%) received a T-DM1 based therapy. The most common regimens across 1L included pertuzumab+trastuzumab+taxane (THP) (38.9%), THP + a platinum agent (7.5%), and T-DM1 (6.1%). From start of 1L, overall median TTD was 10.8 months (95% confidence interval [CI]: 10.1-11.5), median rwPFS was 11.5 months (95% CI: 10.8-12.3), and median rwOS was 40.3 months (95% CI: 37.8-43.4). Among the 1,607 patients who received any T-based regimen in 1L, 496 (30.9%) received T-DM1, 175 (10.9%) received a T-based regimen again, 78 (4.9%) received any other HER2-based regimen, 59 (3.7%) received hormonal therapy alone and 33 (2.1%) received chemotherapy. The most common regimens across 2L (n=1,159) were T-DM1 monotherapy (35.7%), THP (11.2%), and T-DM1+hormone therapy (8.0%). From start of 2L, overall median TTD was 8.3 months (95% CI: 7.6-9.0), median rwPFS was 7.4 months (95% CI: 6.8-8.1), and median rwOS was 27 months (95% CI: 25.9-30.0). Conclusions Variability, which may impact outcomes, is observed in treatment approaches for HER2+ mBC. Additionally, more than half the patients on 1L treatment progressed within a year of initiating treatment, highlighting a remaining need for effective therapies that limit progression and maintain clinical benefit in 1L. Citation Format: Clara Lam, Della Varghese, Beth L. Nordstrom, Brian Murphy, Jenna Collins, Sandhya Mehta. Treatment Patterns and Associated Outcomes Among Patients with HER2+ Metastatic Breast Cancer in the United States [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-34.

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