Abstract 337P
Background
The mTORC1 inhibitor everolimus (EVE) in combination with the aromatase inhibitor (AI) exemestane (EXE) is approved for the treatment of hormone receptor-positive, HER2-negative advanced breast cancer (HR+ aBC) patients (pts) whose disease progressed on/after prior Non-Steroidal AI (NSAI) therapy. However, the efficacy of EVE-EXE after tumor progression on Cyclin-Dependent Kinase 4/6 inhibitors (CDK 4/6i) is unknown.
Methods
The EVERMET study is a retrospective, multicenter, Italian study aiming to investigate the impact of precocious metabolic modifications on clinical outcomes in HR+ aBC pts treated with EVE-EXE. Here we report an exploratory sub-analysis to assess EVE-EXE efficacy in pts previously treated with or naïve to CDK 4/6i. Pts were divided in three groups according to the line of EVE-EXE treatment and to previous therapies for advanced disease: A. pts treated with EVE-EXE as second/third line and previous CDK 4/6i-containing treatment as first-line; B. pts treated with EVE-EXE as second/third line and no previous CDK 4/6i; C. pts treated with first-line EVE-EXE. The primary endpoint was Progression Free Survival (PFS), analyzed using the Kaplan-Meier method and Cox proportional-hazard models.
Results
Two hundred seventy-three pts were included, enrolled in 9 cancer centers that reported data regarding prior CDK 4/6i treatment. Of them, 25 pts belonged to group A, 203 pts to group B and 45 pts to group C. Median PFS was 4.9 months (mos) (range: 3.2-10.6), 7.2 mos (range: 6.2-9.1) and 11.7 mos (range: 7.2-13.7) in group A, B and C, respectively (p=0.0084). Multivariable analysis adjusting for clinically relevant variables, namely age, previous adjuvant endocrine treatment, ECOG PS and presence of visceral disease, revealed an hazard ratio of disease progression for group B vs. A of 0.64 (95% CI 0.40-1.04, p=0.07) and group C vs. A of 0.41 (95% CI 0.24 -0.72, p=0.001).
Conclusions
Prior CDK 4/6i-containing treatment is associated with poorer efficacy of EVE-EXE in HR+ aBC patients. Patients treated with EVE-EXE as first-line therapy had the longest PFS. Prospective data are needed to define the role of EVE-EXE in the era of CDK 4/6i.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.