Real-world outcomes from the systemic use of CDK 4/6 inhibitors (CDKIs) in the management of ER positive (+) HER2 negative (-) metastatic breast cancer (mBC).

e13031 Background: The use of CDKIs have transformed the management of ER+HER2- mBC. As the real-world data matures, this project describes patterns in response to systemic therapy that may inform treatment planning and prognostication. Methods: We analysed the ER+HER2- mBC dataset at Nottingham University Hospitals NHS Trust (NUH) generated by reviewing clinical notes, radiology and e-prescribing records to collect clinical data on patients treated with CDKIs between 01/10/2016 - 01/10/2020. Results: 272 patients with a median age of 65 years (30-90 years) were treated with CDKIs (palbociclib 54.0% (n=147); ribociclib 19.5% (n=53); abemaciclib 26.5% (n=72)) in combination with endocrine therapies (letrozole, anastrozole, exemestane and, fulvestrant). Median overall survival was 49.5 months. Treatment with first-line CDKIs (69.8%; n=190) resulted in superior PFS when compared to CDKIs in a ≥ second-line setting (30.2%; n=82) i.e., mPFS 21.3 vs 12.2 months (HR 0.67; 95% CI, 0.47-0.96; P=0.02). Univariate analysis shown in the table below indicates the benefit to PFS from presentations with de novo mBC and the absence of visceral metastases. In patients treated curatively for early breast cancer (EBC), better outcomes were demonstrated in patients presenting with mBC, >12 months versus ≤12 months of completion of adjuvant endocrine therapy i.e., mPFS 28.4 vs 12.1 months (HR 0.50; 95% CI, 0.30-0.84; P=0.004) when treated with first-line CDKIs. A multivariate analysis identified benefit to PFS from first-line therapy with CDKIs (HR 0.70; 95% CI, 0.49-1.01; P=0.05) and presentation with de novo mBC (HR 0.56; 95% CI, 0.37-0.85; P=0.006). The presence of visceral metastases was associated with poorer outcomes (HR 1.52; 95% CI, 1.08-2.15; P=0.01). Conclusions: This analysis confirms the PFS benefit from CDKIs demonstrated in clinical trials is mirrored in the real-world setting. The analysis was not powered to delineate survival benefit between the individual CDKIs. Presentations with mBC following a prior history of EBC, within ≤12 months of completion of adjuvant endocrine therapy, and with visceral metastases may help predict poorer clinical outcomes and may need to be considered when prognosticating and in treatment planning. This analysis is hypotheses-generating and we will confirm our findings in a prospective manner as the dataset is expanded.Table: see text