(CHICAGO, IL) – Adding everolimus (Afinitor) did not significantly improve the efficacy of weekly paclitaxel/bevacizumab in the first-line treatment of HER2-negative metastatic breast cancer, according to the results of a randomized, placebo-controlled phase 2 study reported at the 2012 American Society of Clinical Oncology Annual Meeting.

Activation and amplification of the mTOR protein complex is common in metastatic breast cancer and increases as tumors develop treatment resistance. Everolimus is an mTor inhibitor, previously shown in the BOLERO-2 trial to prolong PFS when added to aromatase inhibitor therapy.

“No differences were observed in any of the efficacy parameters, including progression-free survival [PFS], response duration, overall response rate, and clinical benefit rate,” reported lead author Denise A. Yardley, MD, of the Sarah Cannon Research Institute, Nashville, TN. A total of 112 women received intravenous paclitaxel and bevacizumab plus everolimus (n=55) or placebo (n=57). Median PFS, the primary endpoint, was 9.63 months in the everolimus arm and 9.13 months in the placebo arm, she reported.

Patients received a median of 5 treatment cycles. Complete responses were seen in 4 patients (7%) receiving everolimus and 2 patients (4%) receiving placebo; the overall response rate was 60% in the everolimus arm and 49% in the placebo arm. Clinical benefit rate was 81% and 80%, respectively.


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In this trial, grade 3 mucositis was seen in 13% of patients who received everolimus (vs. none in the placebo arm), which may have contributed to a dose intensity of only 60% of planned, “and this may have adversely affected the efficacy of the paclitaxel/bevacizumab and everolimus regimen,” she reported. No new signals of toxicity were noted with everolimus in combination with weekly paclitaxel plus bevacizumab.

According to Dr. Yardley, results of this trial differ from those of BOLERO-2 and TAMRAD, in which the addition of everolimus to hormonal therapy improved PFS in patients with estrogen receptor-positive metastatic breast cancer. Other differences in the trials, including patient population, amount of previous treatment, and treatment regimen (hormonal vs. chemotherapy) may have also influenced the current trial’s results.

Abstract