OBJECTIVES: Metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor-2 negative (HER2−) breast cancer continues to be a significant cause of cancer-related death. First-line treatment with a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) has become the standard to improve quality of care and delay time to chemotherapy. However, following CDK4/6i progression, prognosis is poor and optimal second line treatment is not clearly defined. This research aims to identify and assess current treatment patterns for patients with HR+/HER2-metastatic breast cancer (MBC) after first-line therapy CDK4/6i progression.

METHODS: We conducted a targeted literature review in PubMed for studies published between January 2017 – December 2023. Studies were selected if patients had HR+, HER2- MBC and initiated a CDK4/6i as first-line therapy. Studies were only selected if subsequent treatment following CDK4/6i progression was reported. Studies reporting CDK4/6i use in clinical trials were excluded.

RESULTS: We identified 189 articles, of which fifty were screened for eligibility. Reports were mainly excluded for not reporting subsequent treatment patterns. We identified eight observational studies, with five of them reporting both second- line progression free survival (PFS) and subsequent treatment, and three studies only reporting subsequent treatment. The most common subsequent treatment therapy was chemotherapy (34%- 70%), and endocrine-based therapy (19%- 57%) was second most common. Chemotherapy based regimens were mainly taxane- based (28%-59%) or capecitabine containing (14%-51%). For those receiving endocrine -based therapy, fulvestrant (25%-58%) and everolimus + exemestante (12%-42%) were most common.

CONCLUSIONS: Although treatment patterns after progression on a first line CDK4/6i vary, suggesting no standard of care for subsequent treatment, chemotherapy was the most common therapy after progression. Prognosis after second- line treatment remains a challenge, and more research and effective treatments options for patients with HR+ HER2- MBC are needed to delay time to chemotherapy.