mTOR Inhibitor Plus Endocrine Therapy in Postmenopausal Women With Advanced ER-Positive, HER2-Negative Breast Cancer


Key Points

  • Median progression-free survival was 22 months.
  • Overall survival at 24 months was 79%. 

In the phase II BOLERO-4 trial reported in JAMA Oncology, Royce et al found that the combination of the mTOR inhibitor everolimus (Afinitor) and endocrine therapy was active in first-line treatment of postmenopausal women with advanced estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer.

Study Details

In the study, 202 patients from 56 centers in 13 countries were enrolled between March 2013 and December 2014 and received first-line treatment of advanced disease with everolimus at 10 mg/d plus letrozole at 2.5 mg/d. Second-line treatment with everolimus at 10 mg/d plus exemestane at 25 mg/d was offered at the investigator’s discretion upon initial disease progression. Patients had a median age of 64.0 years; 96% had metastatic disease and 4% had locally advanced disease; 68% had ≥ 3 metastatic sites; and 61% had visceral metastases.

The primary endpoint was investigator-assessed progression-free survival.

Efficacy Outcomes

Median follow-up was 29.5 months at data cutoff in December 2016. Median progression-free survival was 22.0 months in first-line treatment. Median overall survival was not reached, with 24-month overall survival estimated at 78.7%.  Among 50 patients who received second-line treatment, median progression-free survival was 3.7 months.

Adverse Events

In the first-line setting, the most common adverse events of any grade were stomatitis (69%), decreased weight (44%), and diarrhea (41%). The most common grade 3 or 4 adverse event was anemia (10%). Serious adverse events occurred in 31% of patients, with the most common being pneumonia (4.5%). Adverse events led to treatment discontinuation in 25%, with stomatitis being the most common reason (3.5%). In the second-line setting, the most common adverse events of any grade were stomatitis and decreased weight (20% each), and the most common grade 3 or 4 adverse event was hypertension (10%).

The investigators concluded, “The results of this trial add to the existing body of evidence suggesting that everolimus plus endocrine therapy is a good first-line treatment option for postmenopausal women with [ER-positive, HER2-negative] advanced breast cancer.”

The study was supported by Novartis Pharmaceuticals Corporation.

Melanie Royce, MD, PhD, of the University of New Mexico Comprehensive Cancer Center, Albuquerque, is the corresponding author for the JAMA Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.