Everolimus (EVE) combined with exemestane (EXE) is currently approved for treating patients with metastatic hormone receptor–positive breast cancer (mHRBC) who no longer respond to nonsteroidal aromatase inhibitors (NSAIs). Notably, the BOLERO-2 trial, which supported this approval, did not include patients who had previously received CDK4/6 inhibitors (CDK4/6is), now widely used as first-line therapy for mHRBC. Therefore, the benefits and clinical outcomes of EVE plus EXE in patients with prior CDK4/6i exposure have yet to be established. We conducted a retrospective analysis of adult patients with metastatic hormone receptor–positive breast cancer (mHRBC) at our center who had disease progression following treatment with either a nonsteroidal aromatase inhibitor (NSAI) alone or in combination with a CDK4/6 inhibitor, and who subsequently received at least one cycle of everolimus (EVE) plus exemestane (EXE) between 2012 and 2018. Information collected included patient demographics, prior therapies, adverse events, and treatment outcomes. The study primarily aimed to assess differences in progression-free survival (PFS) and overall survival (OS) between patients with prior NSAI plus CDK4/6 inhibitor therapy and those who received NSAI monotherapy. Of the 43 patients analyzed, 17 had previously received CDK4/6 inhibitors. Apart from differences in the incidence of de novo metastatic disease, the two groups were largely comparable in terms of patient demographics and disease characteristics. Median progression-free survival was 3.6 months for the CDK4/6i-exposed group versus 4.2 months for those without prior exposure, while median overall survival was 15.6 months versus 11.3 months, with no statistically significant differences observed between the cohorts. Previous treatment with CDK4/6 inhibitors did not affect survival outcomes in patients with metastatic hormone receptor-positive breast cancer receiving everolimus combined with exemestane. Nevertheless, a trend toward better overall survival was observed in the CDK4/6 inhibitor-treated group, warranting further assessment in larger patient populations. The combination of CDK4/6 inhibitors with a nonsteroidal aromatase inhibitor has established itself as the standard first-line treatment for metastatic hormone receptor-positive breast cancer. Everolimus combined with exemestane is an approved therapy in subsequent lines; however, the pivotal data supporting this regimen were generated before CDK4/6 inhibitors became available. Consequently, the clinical efficacy of everolimus plus exemestane following prior CDK4/6 inhibitor treatment remained unclear. This retrospective cohort study provides real-world evidence indicating that previous exposure to CDK4/6 inhibitors does not adversely affect survival outcomes with everolimus plus exemestane.
