Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy

Abstract

Background: There is currently no clinical trial data regarding the efficacy of everolimus exemestane (EE) following prior treatment with CDK4/6 inhibitors (CDK4/6i). This study assesses the use and efficacy of everolimus exemestane in patients with metastatic HR+ HER2- breast cancer previously treated with endocrine therapy (ET) or endocrine therapy + CDK4/6i.

Methods: Retrospective analysis of electronic health record-derived data for HR+ HER2- metastatic breast cancer from 2012 to 2018. The proportion of patients receiving EE first-line, second-line, or third-line, and the median duration of EE prior to next line of treatment (TTNT) by line of therapy was calculated. OS for patients receiving EE first-line, second-line, or third-line, indexed to the date of first-line therapy initiation and stratified by prior treatment received, was calculated with Kaplan-Meier method with multivariable Cox proportional hazards regression analysis.

Results: Six hundred twenty-two patients received EE first-line (n = 104, 16.7%), second-line (n = 273, 43.9%) or third-line (n = 245, 39.4%). Median TTNT was 8.3 months, 5.5 months, and 4.8 months respectively. Median TTNT of EE second-line was longer following prior ET alone compared to prior ET + CDK4/6i (6.2 months (95% CI 5.2, 7.3) vs 4.3 months (95% CI 3.2, 5.7) respectively, p = 0.03). Similarly, EE third-line following ET alone vs ET + CDK4/6i in first- or second-line resulted in median TTNT 5.6 months (95% CI 4.4, 6.9) vs 4.1 months (95% CI 3.6, 6.1) respectively, although this was not statistically significant (p = 0.08). Median OS was longer for patients who received EE following prior ET + CDK4/6i. EE second-line following ET + CDK 4/6i vs ET alone resulted in median OS 37.7 months vs. 32.7 months (p = 0.449). EE third-line following ET + CDK4/6i vs prior ET alone resulted in median OS 59.2 months vs. 40.8 months (p < 0.010). This difference in OS was not statistically significant when indexed to the start of EE therapy.

Conclusion: This study suggests that EE remains an effective treatment option after prior ET or ET + CDK4/6i use. Median TTNT of EE was longer for patients who received prior ET, whereas median OS was longer for patients who received prior ET + CDK4/6i. However, this improvement in OS was not statistically significant when indexed to the start of EE therapy suggesting that OS benefit is primarily driven by prior CDK4/6i use. EE remains an effective treatment option regardless of prior treatment option.

Keywords: CDK4/6 inhibitors; Endocrine therapy; Everolimus; Exemestane; Metastatic hormone-positive HER2-negative breast cancer; Sequence of therapy; Targeted therapy.

Fig. 1

Study population: patients diagnosed with hormone receptor-positive HER2-negative metastatic breast cancer from 2012 to 2018 who received everolimus exemestane in first-line, second-line, or third-line

Fig. 2

Treatment comparison groups for analyzing the duration of therapy and overall survival

Fig. 3

Proportion of patients with hormone receptor-positive HER2-negative metastatic breast cancer receiving everolimus exemestane as first-, second-, and third-line treatment from 2012 to 2018

Fig. 4

a Kaplan-Meier curves for patients receiving everolimus exemestane as second-line treatment, stratified by prior therapy. b Kaplan-Meier curves for patients receiving everolimus and exemestane as third-line treatment, stratified by prior therapy

Fig. 5

Overall survival calculated using the date of start of everolimus exemestane treatment: a Kaplan-Meier curves for patients receiving everolimus exemestane as second-line treatment, stratified by prior therapy; b Kaplan-Meier curves for patients receiving everolimus exemestane as third-line treatment, stratified by prior therapy