Abstract PS5-01-26: Long-term outcomes of first-line (1L), guideline-recommended treatment versus alternative regimens in HER2+ metastatic breast cancer (mBC): a retrospective observational study of US electronic health records

Abstract Background: The current guideline-recommended 1L standard of care (SOC) for HER2+ mBC is taxane, trastuzumab, and pertuzumab (THP) followed by maintenance therapy after initial response; however, many patients may not receive SOC in routine clinical practice. This study describes demographics, disease characteristics, and long-term treatment outcomes in US patients treated with SOC or other treatments for 1L HER2+ mBC. Methods: This retrospective observational study used the nationwide Flatiron Health database of derived and de-identified electronic health records. Patients aged ≥18 years with HER2+ mBC who received 1L treatment for mBC from January 2015 to February 2024 (excluding clinical trial drugs), with confirmatory HER2+ biomarker test results before initiation of 1L treatment, were included. Demographic and clinical characteristics were captured on the index date (start of 1L treatment). Patients were followed until death or last activity date on or before end of study (September 2024). SOC was defined as THP followed by maintenance trastuzumab/pertuzumab after response (with concurrent endocrine therapy for hormone receptor-positive HR+ disease). Study outcomes included real-world time from initiation of 1L treatment to initiation of 3L treatment or death (rwTTNT2) and real-world time from initiation of 1L treatment to disease progression after initiation of 2L treatment or death (rwPFS2). Results: Overall, 3277 patients were included; 1L SOC was received by 35.5% (n=1164) of patients, with mean (standard deviation) age at index date of 58.7 (12.4) years, compared with 61.4 (14.1) years for other regimens (see Table for further characteristics). Of the 64.5% (n=2113) of patients who received other regimens, 17.1% (n=362) received HER2-targeted monotherapy and 36.8% (n=778) HER2-targeted combination therapy. Recurrent disease and HR+ status were observed in a greater proportion of patients treated with other regimens than with SOC. During follow up, 32.9% of patients treated with 1L SOC were observed to receive 3L treatment, 26.5% died, and 40.6% were censored before 3L. In patients receiving other regimens at 1L, these proportions were 37.1%, 33.3%, and 29.6%, respectively. Median rwTTNT2 (95% CI) was prolonged in patients treated with 1L SOC versus other regimens (30.1 27.4, 33.6 vs 17.4 16.1, 19.0 months). Median rwPFS2 (95% CI) was also prolonged in patients treated with 1L SOC (26.1 24.2, 28.0 months) versus other regimens (18.9 17.7, 19.9 months). Conclusion: Among patients with HER2+ mBC, receipt of guideline-recommended SOC (vs not) in the 1L setting was associated with substantially prolonged long-term outcomes. However, disease characteristics at treatment initiation may have influenced treatment regimen choice and impacted long-term outcomes. Citation Format: M. Inoue-Choi, B. Adeyemi, J. Schmidt, L. Luo, A. Ali. Long-term outcomes of first-line (1L), guideline-recommended treatment versus alternative regimens in HER2+ metastatic breast cancer (mBC): a retrospective observational study of US electronic health records abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-26.