Efficacy Study of Everolimus and Exemestane for the Treatment of Patients with Metastatic Hormone Receptor–Positive Breast Cancer Previously Treated with CDK4/6 Inhibitors

In patients with metastatic hormone receptor–positive breast cancer treated previously with a CDK4/6 inhibitor, there was a lower median progression-free survival benefit from everolimus in combination with exemestane compared with those patients who had not received this combination.

Based on the BOLERO-2 trial, the US Food and Drug Administration initially approved everolimus in combination with exemestane to treat patients with metastatic hormone receptor–positive breast cancer who have previously been treated with nonsteroidal aromatase inhibitors.

While CDK4/6 inhibitors have become standard of care for metastatic hormone receptor–positive breast cancer, none of the patients in the BOLERO-2 trial received previous treatment with CDK4/6 inhibitors. In patients with metastatic hormone receptor–positive breast cancer who were previously treated with CDK4/6 inhibitors, there is a lack of data to support the use of everolimus plus exemestane.

Between January 1, 2012, and April 1, 2020, Hanjie Mo, PharmD, BCOP, Clinical Pharmacy Specialist-Solid Tumor, Hematology/Oncology, Cleveland Clinic, OH, and colleagues at the Cleveland Clinic and the University Hospitals Seidman Cancer Center, Cleveland, evaluated patients aged ≥18 years with metastatic hormone receptor–positive breast cancer who were treated with everolimus plus exemestane. If patients received everolimus plus exemestane for <30 days, they were excluded.

Patient and tumor characteristics, previous therapies received in the metastatic setting, adverse event history, and clinical outcomes were part of the collected data set.

The primary goal of the study was to compare between patients with and without previous exposure to CDK4/6 inhibitors and progression-free survival (PFS) outcomes for patients who received everolimus in combination with exemestane. Overall survival and safety were considered secondary outcomes.

Included in the study were 192 patients, of which 79 patients had received previous treatment with a CDK4/6 inhibitor, while 113 patients had not. Between these 2 groups, there was similar baseline histology, bone-only disease, presence of lung or liver metastases, menopause status, and de novo metastatic disease. Before receiving everolimus plus exemestane in both groups, 2 lines of treatment in the metastatic setting was the median. A smaller number of patients were treated with previous chemotherapy in the metastatic setting than those who were treated with previous CDK4/6 inhibitor therapy (32.9% vs 49.6%; P = .032).

A significant difference between the groups was not detected when analyzing OS outcomes. In patients who were previously treated with CDK4/6 inhibitor therapy, median PFS was 3.9 months (95% confidence interval [CI], 3.5-4.8) compared with 5.5 months (95% CI, 4.0-6.3) in the group of patients who did not receive previous treatment with CDK4/6 inhibitors (HR for progression, 1.46; 95% CI, 1.08-1.97; P = .013). Due to tolerability concerns or adverse drug events, 16% (N = 32) of patients discontinued everolimus in combination with exemestane. The researchers concluded that patients who were treated previously with a CDK4/6 inhibitor had a lower median PFS benefit from everolimus in combination with exemestane compared with those patients who had not received this combination.

Source: Mo H, Renna CE, Moore HCF, et al. Efficacy of everolimus and exemestane for the treatment of metastatic hormone receptor-positive breast cancer in patients previously treated with CDK4/6 inhibitors. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS12-18.