Abstract PS12-18: Efficacy of everolimus and exemestane for the treatment of metastatic hormone receptor-positive breast cancer in patients previously treated with CDK4/6 inhibitors

Background: Everolimus in combination with exemestane (EVE+EXE) was initially FDA approved to treat metastatic hormone receptor-positive breast cancer (mHRBC) in patients previously treated with nonsteroidal aromatase inhibitors based on the BOLERO-2 trial. However, none of the patients in the BOLERO-2 trial received prior CDK4/6 inhibitors, which have become standard of care for mHRBC. There is limited data to support the use and clinical benefit of EVE+EXE in mHRBC patients previously treated with CDK4/6 inhibitors. Methods: We reviewed patients ≥18 years old with mHRBC treated with EVE+EXE at our institution from January 1, 2012, to April 1, 2020. Patients were excluded if they received EVE+EXE ≤30 days. Data collected included patient and tumor characteristics, prior therapies in the metastatic setting, adverse drug events, and clinical outcomes. The primary objective was to compare progression free survival (PFS) for EVE+EXE between patients with and without prior exposure to CDK4/6 inhibitors. Secondary outcomes included overall survival (OS) and safety. Group comparisons were performed by two-sample t test or Wilcoxon rank sum test for continuous variables and Pearson’s chi-square test or Fisher’s exact test for categorical variables. Log-rank test was used to compare the PFS and OS between groups. Results: One-hundred ninety two patients were included in the study; 79 patients had received prior CDK4/6 inhibitor based therapies, while 113 patients did not. Baseline patient characteristics such as histology, menopause status, de novo metastatic disease, presence of lung or liver metastases, and bone only disease were similar between groups. There was a median of 2 lines of treatment in the metastatic setting prior to receiving EVE+EXE in both groups. Fewer patients received prior chemotherapy in the metastatic setting in those who received prior CDK4/6 inhibitors (32.9% vs 49.6%, p=0.032). In patients who received a prior CDK4/6 inhibitor, median PFS was 3.9 months (95% CI: 3.5 to 4.8) compared to 5.5 months (95% CI: 4.0 to 6.3) in those who did not receive a prior CDK4/6 inhibitor (HR for progression, 1.46; 95% CI: 1.08 to 1.97, p=0.013). Overall survival between groups was not significantly different. A total of 32 (16.7%) patients discontinued EVE+EXE due to intolerance or adverse drug events. Conclusion: Patients who received a prior CDK4/6 inhibitor had a lower median PFS benefit from EVE+EXE compared to those who did not. Citation Format: Hanjie Mo, Catherine E Renna, Halle CF Moore, Jame Abraham, Megan L Kruse, Alberto J Montero, Susan B LeGrand, G Thomas Budd. Efficacy of everolimus and exemestane for the treatment of metastatic hormone receptor-positive breast cancer in patients previously treated with CDK4/6 inhibitors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-18.