Treatment Patterns and Clinical Outcomes in Metastatic HR+/HER2- and Triple-Negative Breast Cancer in Canada: The HER2- TRENDS Study.

The treatment landscape for human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) in Canada is rapidly evolving. This retrospective cohort study described real-world historical treatment patterns and clinical outcomes for patients with HER2- mBC. Adults enrolled in the pan-Canadian 'Personalize My Treatment' cancer registry and diagnosed with stage IV HER2- mBC (01/01/2015-03/01/2022) were eligible and followed until 03/01/2023. Hormone receptor-positive (HR+)/HER2- mBC and triple-negative mBC (mTNBC) were analyzed separately and further stratified by line of therapy. Main study outcomes included treatment patterns, PIK3CA/AKT1/PTEN alteration testing/positivity rates, and overall survival (OS), all analyzed descriptively. A total of 507 patients with HER2- mBC were included (HR+/HER2- mBC: 387; mTNBC: 120; median follow-up: 54.1 months). The most common HR+/HER2- mBC treatments were cyclin‑dependent kinase 4/6 inhibitors (CDK4/6is) plus endocrine therapy (ET) in first line (1L; 55.0%), targeted therapies (22.9%) and CDK4/6i + ET (22.0%) in second line (2L), and chemotherapy (CT) monotherapy (42.7%) in third line (3L). CT monotherapy was the most common mTNBC treatment in 1L (35.1%), 2L (50.6%), and 3L (54.8%). Attrition was similar for HR+/HER2- mBC and mTNBC from 1L-2L (16.9% and 16.3%, respectively) but was lower for HR+/HER2- mBC from 2L-3L (33.2% and 38.6%) and 3L-4L (48.1% and 62.1%). PIK3CA/AKT1/PTEN alteration testing was performed in 31.8% of patients with HR+/HER2- mBC and 50.0% with mTNBC, with alterations identified in 15.4% and 20.0% of patients, respectively. Median OS (65.9 and 31.4 months, respectively), OS rates (1 year: 94.8% and 79.8%; 5 years: 56.0% and 21.7%), and time to next treatment (1L-2L: 24.5 and 8.1 months; 2L-3L: 10.1 and 5.1 months) were greater for HR+/HER2- mBC than mTNBC. These findings describe historical HER2- mBC treatment patterns and associated outcomes in Canada. Ongoing research is needed to optimize therapeutic strategies, expand novel treatment access, and improve patient outcomes.