Real world data on first-line systemic therapy for hormone receptor positive HER2 negative metastatic breast cancer: a trend shift in the era of CDK 4/6 inhibitors

ABSTRACT Hormone receptor-positive (HR+) human epidermal growth factor receptor-2 (HER2)-negative tumors represent the most common subtype of metastatic breast cancer. International guidelines such as those from ASCO, NCCN and ABC4 clearly state that ET should be considered the preferred first-line therapy for these patients in the absence of very symptomatic visceral disease or evidence of endocrine resistance. Nonetheless compliance with guidelines vary significantly all over the world for many different reasons. Historically, a substantial proportion of patients with HR positive, HER2 negative metastatic breast cancer have been treated with chemotherapy in first-line setting, jeopardizing patients’ quality of life without a significant benefit in outcome. In 17 observational studies, including more than 63,000 patients, ET was most frequently used in first-line treatment for HR+/HER2- MBC (range 42-87%), nonetheless a high proportion of patients received CT (13-66%) as initial therapy. More recently, results of clinical trials with CDK 4/6 inhibitors improved response, progression-free and overall survival in this population and are currently the standard of care. There was a trend towards increase use of ET in recent years. This review article aims to evaluate real-world data (RWD) on patterns of first-line treatment for HR+ HER2- MBC with a special focus on the use of CT in this setting and the potential implications and perceived preliminary changes after the introduction of CDK4/6 inhibitors.