Everolimus plus exemestane treatment in metastatic hormone receptor-positive breast cancer patients previously treated with CDK4/6 inhibitor therapy

Background: The combination of everolimus (EVE) and exemestane (EXE) is approved for the treatment of metastatic hormone receptor-positive breast cancer (mHRBC) patients who progress on non-steroidal aromatase inhibitor (NSAI) therapy. However, none of the subjects enrolled in the trial that led to this approval (BOLERO-2) had previously received CDK4/6 inhibitors (CDK4/6is), which have since become a frontline standard of care for mHRBC. As such, the clinical benefit of EVE + EXE in patients who have previously received CDK4/6is remains unknown.

Methods: Adult mHRBC patients at our institution who progressed on a NSAI + CDK4/6i or NSAI therapy alone and were treated with at least one cycle of EVE + EXE between 2012 and 2018 were analyzed. Collected data included patient demographics, treatment history, adverse events, and clinical outcomes. Primary objectives were to compare progression-free survival (PFS) and overall survival (OS) between patients who received prior NSAI + CDK4/6i therapy versus a NSAI alone.

Results: Among 43 patients, 17 had prior CDK4/6i exposure. With the exception of de novo metastatic disease, patient and disease characteristics were comparable across treatment cohorts. There was no significant difference in PFS (median 3.6 vs 4.2 months) or OS (median 15.6 vs 11.3 months) between patients who had received prior CDK4/6is and those who had not, respectively.

Conclusion: Prior exposure to CDK4/6i therapy did not impact survival outcomes for mHRBC patients taking EVE + EXE. However, there was a trend towards improved OS in the CDK4/6i cohort that should be evaluated in larger cohorts.

Implications for practice: The use of CDK4/6 inhibitors in combination with a non-steroidal aromatase inhibitor has become a standard frontline therapy in metastatic hormone receptor-positive breast cancer. An approved subsequent line of therapy is everolimus plus exemestane however the original data supporting this therapy predated prior of approval CDK4/6 inhibitors. As such, the clinical benefit of everolimus and exemestane in patients previously treated with a CDK4/6i was unknown. This retrospective cohort study offers real world data demonstrating prior CDK4/6 inhibitor exposure does not impact survival outcomes for everolimus plus exemestane.

Keywords: CDK4/6 inhibitors; Everolimus plus exemestane; Metastatic hormone receptor-positive breast cancer; cohort studies.