Everolimus plus letrozole is efficacious as a first-line treatment regimen for patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to a study presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1

The phase 3 BOLERO-2 trial established that everolimus combined with exemestane prolongs progression-free survival compared with exemestane plus placebo in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer that progressed on endocrine therapy.

For the phase 2 BOLERO-4 trial (ClinicalTrials.gov Identifier: NCT01698918), researchers evaluated the efficacy and safety of everolimus plus exemestane among patients with ER-positive, HER2- metastatic or locally advanced breast cancer.

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Investigators enrolled 202 patients who had not received prior therapy for advanced disease to receive everolimus plus letrozole. Upon disease progression, patients were eligible to receive everolimus plus exemestane until further progressive disease or unacceptable toxicity.

Median progression-free survival was not reached at the median follow-up of 17.5 months. Researchers estimated the 6-month and 12-month progression-free survival rates to be 83.6% (95% CI, 77.3-88.2) and 71.4% (95% CI, 64.0-77.5), respectively.

The overall response rate was 42.6% (95% CI, 35.7-49.7) the clinical benefit rate for the combination was 74.3% (95% CI, 67.7-80.1).

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The most frequently reported adverse events were stomatitis, which was experienced by 67.8% of patients, as well as weight loss and diarrhea.

The study is evaluating whether an alcohol-free dexamethasone mouth rinse can help to reduce the severity of oral stomatitis.              


  1. Royce M, Villanueva C, Ozguroglu M, et al. BOLERO-4: Phase 2 trial of first-line everolimus (EVE) plus letrozole (LET) in estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (BC). Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.