Real-world time trends in overall survival, treatments and patient characteristics in HR+/HER2− metastatic breast cancer: an observational study of the SONABRE Registry

BACKGROUND: This study aims to evaluate whether changes in therapeutic strategies have improved survival of patients diagnosed with hormone receptor positive (HR+), HER2 negative (HER2−) advanced breast cancer (ABC) in real-world. METHODS: All 1950 patients systemically treated for HR+/HER2− ABC and diagnosed between 2008 and 2019 in eight hospitals were retrieved from the SONABRE Registry (NCT-03577197). Patients were categorized per three-year cohorts based on year of ABC diagnosis. Tests for trend were used to examine differences in baseline characteristics, Kaplan–Meier methods and Cox proportional hazards for survival analyses, and competing-risk methods for 3-year use of systemic therapy. FINDINGS: Over time, patients were older (≥70 years, 37%, n = 169/456 in 2008–2010, 47%, n = 233/493 in 2017–2019, p = 0.004) and more often had multiple metastatic sites at ABC diagnosis (48%, n = 220/456 in 2008–2010, 56%, n = 275/493 in 2017–2019, p = 0.002). Among patients with metachronous metastases the prior exposure to (neo-) adjuvant therapies increased over time (chemotherapy, 38%, n = 138/362 in 2008–2010, 48%, n = 181/376 in 2017–2019, p = <0.001; endocrine therapy, 64%, n = 231/362 in 2008–2010, 72%, n = 271/376 in 2017–2019, p = <0.001). Overall survival significantly improved from median 31.1 months (95% CI:28.2–34.3) for patients diagnosed in 2008–2010 to 38.4 months (95% CI:34.0–41.1) in 2017–2019 (adjusted hazard ratio = 0.76, 95% CI:0.64–0.90; p = 0.001). Three-year use of CDK4/6 inhibitors increased from 0% for patients diagnosed in 2008–2010 to 54% for diagnosis in 2017–2019. Conversely, three-year use of chemotherapy was 50% versus 36%, respectively. INTERPRETATION: Over time, patients diagnosed with HR+/HER2− ABC presented with less favourable patient characteristics. Nevertheless, we observed that overall survival of ABC increased between 2008 and 2019, with increased use of endocrine/targeted therapies. FUNDING: The SONABRE Registry is supported by the Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); 10.13039/100004336Novartis BV; 10.13039/100004337Roche; 10.13039/100004319Pfizer; and 10.13039/100004312Eli Lilly & Co. Funding sources had no role in the writing of the manuscript.