Abstract P1-19-12: Patterns of treatment with everolimus and exemestane in hormone receptor positive HER2 negative metastatic breast cancer in the era of targeted therapy
Authors: Rozenblit Mariya , Pusztai Lajos , Adelson Kerin , Mougalian Sarah 
Published: March 2020

Background: In 2012 the FDA approved everolimus and exemestane (EE) as second line therapy for patients who have progressed on letrozole or anastrozole, based on the BOLERO-2 trial which showed improvement in PFS with EE compared to exemestane alone (6.9 vs 2.8 months). Currently, aromatase inhibitors (AI), or fulvestrant (F), alone or in combination with a CDK4/6 inhibitor (CDK4/6i) are the most commonly used first line endocrine therapies for hormone receptor (HR) positive HER2 negative metastatic breast cancer (mBC). There is currently no clinical trial data regarding the efficacy of EE in patients previously treated with CDK4/6i. The goal of this project was to explore the treatment patterns of EE in this contemporary patient population, with particular interest in those who had received prior CDK4/6i plus AI/F, as first, second, or third-line treatment.

Methods: The Flatiron Health electronic health record-derived nationwide database selected de-identified patients with HR positive HER2 negative mBC and the first (1L), second (2L), and third line (3L) treatments they received. Duration of treatment (DOT) is defined as time from the date of initiation of a line of treatment to the day prior to initiation of subsequent line of treatment; prolonged DOT is defined as duration ≥ 6 months. Medical non-cancer co-morbidities listed as defined by the Charlson Comorbidity Index were included. Median DOT was compared using t-test, unadjusted for patient and disease characteristics. Statistical analysis was performed using Python v3.7.

Results: A total of 8457 HR positive HER2 negative patients diagnosed with mBC between 1/2011 and 1/2019 were identified. Of these, 726 patients received EE in 1L (N=127), 2L (N=326), or 3L (N=273). In this cohort, 72.3% of patients were diagnosed between 2011-2014, and 27.7% were diagnosed after 1/2015, and most (94.6%) were treated in the community setting. The majority were female (98.4%), Caucasian (75.1%), and had no co-morbidities (79%); the mean age was 64. A quarter of patients (25%) had de novo mBC. The median DOT for 1L EE was 7.6 months (95% CI 5.6, 9.6); 56.7% received 1L EE for ≥6 months. The median DOT for 2L EE was 9.1 months (95% CI 7.6,10.6) following 1L AI/F and 10.7 months (95% CI 8.5,12.9) following 1L AI/F plus CDK4/6i (p&lt;0.02). Over half (52%) of patients received 2L EE for ≥6 months following 1L AI/F, and 32% received 2L EE for ≥6 months following 1L AI/F plus CDK4/6i (p&lt;0.005). The median DOT for 3L EE was 5.6 months (95% CI 3.8, 7.3) following 2L AI/F 2L vs 4.1 months (95% CI 3.1, 5.0) following 2L AI/F plus CDK4/6i (p&lt;0.01). 48.5% received 3L EE for ≥6 months following 2L AI/F vs 34.2% following 2L AI/F plus CDK4/6i (p=0.06).

Conclusion: In a cohort of patients with HR positive HER2 negative mBC who received EE in the 2L or 3L, a significant percentage of patients derived clinical benefit (DOT&gt;6 months) from EE, even after CDK4/6i therapy. Patients who received CDK4/6i 1L had longer unadjusted DOT of 2L EE compared to those who received 1L AI/F alone.

NMedian DOT (mo), 95% CIProlonged DOT (%)1L EE1277.6 (95% CI 5.6, 9.6)56.7%1L AI/F→2L EE2009.1 (95% CI 7.6, 10.6)52.0%1L AI/F + CDK4/6i→2L EE5010.7 (95% CI 8.5, 12.9)32.0%2L AI/F→3L EE995.6 (95% CI 3.8, 7.3)48.5%2L AI/F + CDK4/6i→3L EE734.1 (95% CI 3.1, 5.0)34.2%

Citation Format: Mariya Rozenblit, Lajos Pusztai, Kerin Adelson, Sarah Mougalian. Patterns of treatment with everolimus and exemestane in hormone receptor positive HER2 negative metastatic breast cancer in the era of targeted therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-12.