Although progression-free survival was not significantly different between everolimus or placebo in combination with trastuzumab plus paclitaxel, the addition of everolimus notably prolonged progression-free survival in the HR-negative, HER2-positive population, a new study published online ahead of print in the journal The Lancet Oncology has shown.

For the international, double-blind, controlled, phase III trial, researchers enrolled 719 patients with locally assessed HER2-positive advanced breast cancer who had not received previous treatment for advanced disease. 

Participants were randomly assigned 2:1 to receive everolimus once daily or placebo plus weekly trastuzumab and paclitaxel on days 1, 8, and 15 of each 28-day cycle.

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Results showed that median progression-free survival was 14.95 months (95% CI: 14.55, 17.91) with everolimus compared with 14.49 months (95% CI: 12.29, 17.08) with placebo (HR = 0.89; 95% CI: 0.73, 1.08; P=0.1166).

Researchers found that in the HR=negative subpopulation, the addition of everolimus prolonged progression-free survival by 7.2 months (HR = 0.66; 95% CI: 0.48, 0.91; P=0.0049), but this was not statistically significant.

In regard to safety, the most common adverse events associated with everolimus use were stomatitis, diarrhea, and alopecia.

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The most frequently reported grade 3 or 4 adverse events with everolimus were neutropenia, stomatitis, anemia, and dirrhea. Four percent of patients in the everolimus group died as a result of a treatment-related adverse event compared with none in the placebo group.

The findings suggest that the addition of everolimus to paclitaxel and weekly trastuzumab should be studied further as first-line treatment for patients with HR-negative, HER2-positive advanced breast cancer.


  1. Hurvitz SA, Andre F, Jiang Z, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. J Clin Oncol. 2015. [Epub ahead of print]. doi: 10.1016/S1470-2045(15)00051-0.