Abstract PO1-16-07: Patient Characteristics and Treatment Sequencing Among HER2-low Metastatic Breast Cancer Patients with Rapid vs. Delayed Progression on First-line Endocrine Therapy
Authors: Tan Chia Jie , Willis Connor , Au Trang , Schabath Matthew , Li Chenghui , Kelley Kristen , Xu Xiaoqing , Park Leah , Lam Clara , Mehta Sandhya , Kwong Jackie , Brixner Diana , Stenehjem David 
Published: May 2024

Abstract
Background Patients with HER2-low (IHC 1+ or 2+ and negative ISH) and hormone-receptor positive (HR+) metastatic breast cancer (mBC) who rapidly progress on first-line (1L) endocrine therapy may experience different treatment pathways than those with delayed progression. The goal of this multisite study is to describe the characteristics, treatment patterns and outcomes of these patients with rapid vs. delayed progression. Methods This was a retrospective cohort study of HER2-low, HR+, mBC patients who received 1L endocrine-based treatment regimen at the Huntsman Cancer Institute, Moffitt Cancer Center, and the Winthrop P. Rockefeller Cancer Institute between 2017 and 2021. With no conventional definition, our study defined rapid progression as disease progression within 12 months of 1L treatment initiation vs &gt;12 months/no progression during study follow-up as delayed progression. Demographic and clinical characteristics, and 1L and second-line (2L) treatment patterns were assessed using descriptive statistics. Using Kaplan-Meier analysis, overall survival (OS) was estimated from treatment initiation to death while progression-free survival (PFS) was estimated from treatment initiation to death or disease progression according to physician notes in patients’ charts. Censoring was performed at the date of last follow-up or 31 Dec 2021, whichever occurred earlier. Results The study included 118 patients who received 1L endocrine therapy (see table), mostly in combination with a CDK4/6 inhibitor (n = 87, 73.7%). Rapid progression was observed for 25 (21.2%) patients with a median 1L PFS and OS of 6.4 months (95% CI: 5.4-8.2) and 20.5 months (95% CI: 14.4-30.5), respectively, compared to delayed progressors (median 1L PFS = 30.5 months, 95% CI: 21.5-54.2 and median OS = 62.1 months, 95% CI: 46.4 -upper bound not reached). Rapid progressors were more likely than delayed progressors to be current smokers (n = 6, 24.0% vs n = 7, 7.5%, p = 0.015) or had liver metastasis at diagnosis of advanced disease (n = 11, 44.4% vs n = 17, 18.3%, p = 0.007) but less likely to have bone as the only metastasis site (n = 6, 24.0% vs n = 46, 49.5%, p = 0.023). A smaller proportion of rapid progressors were on CDK4/6 inhibitors in 1L (n = 17, 68.0%) compared to delayed progressors (n = 70, 75.3%) but the difference was not statistically significant. A substantial proportion of rapid progressors (68%, n = 17) continued to receive endocrine therapy in 2L, including endocrine therapy alone (n = 6, 24.0%), endocrine therapy with targeted therapy (n = 6, 24.0%) and endocrine therapy with CDK4/6 inhibitors (n = 5, 20.0%). Among patients on 1L endocrine therapy who continued to a 2L treatment, 2L PFS and OS of rapid progressors (n = 24) were 5.7 months (95% CI: 3.2-10.6) and 14.1 months (95% CI: 6.8-24.2), respectively, compared to 9.2 months (95% CI: 3.1-13.7) and 29.2 months (95% CI:14.4- upper bound not reached) among delayed progressors (n = 39). Conclusion In this study of patients with HER2-low and HR+ mBC, many patients with rapid disease progression on 1L endocrine-based regimens continued to receive endocrine therapy in their next line of therapy and experienced poor clinical outcomes. This preliminary chart review study highlights the unmet need for more effective treatments for patients with rapid progression on 1L endocrine-based regimens. Further research with a larger sample size is warranted to confirm these findings.
Patient characteristics and treatment patterns
Demographic characteristics and treatment patterns of stage IV breast cancer patients with HER2-low disease and received 1L endocrine therapy
Citation Format: Chia Jie Tan, Connor Willis, Trang Au, Matthew Schabath, Chenghui Li, Kristen Kelley, Xiaoqing Xu, Leah Park, Clara Lam, Sandhya Mehta, Jackie Kwong, Diana Brixner, David Stenehjem. Patient Characteristics and Treatment Sequencing Among HER2-low Metastatic Breast Cancer Patients with Rapid vs. Delayed Progression on First-line Endocrine Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-07.