Everolimus provides new treatment option for advanced breast cancer
MedWire News: Adding everolimus to exemestane chemotherapy significantly prolongs progression-free survival among postmenopausal women with previously treated advanced breast cancer, results of the BOLERO-2 trial show.
The study was hailed as "the beginning of a new era for patients with advanced breast cancer" at the 2011 European Multidisciplinary Cancer Congress.
José Baselga (Harvard Medical School, Boston, Massachusetts, USA) explained that BOLERO-2 (Breast cancer trials of OraL EveROlimus-2) tested the effect of adding the mammalian target of rapamycin (mTOR) inhibitor everolimus 10 mg/day or placebo to exemestane 25 mg/day in 724 postmenopausal women with estrogen-receptor-positive (ER+), HER2-negative advanced breast cancer. All women had become refractory to either letrozole or anastrozole.
The trial was stopped early, in February 2011, after an interim analysis found clear evidence of benefit in the everolimus group. Progression-free survival (PFS), the study's primary endpoint, was 2.8 months with placebo versus 6.9 months with exemestane, giving a highly significant hazard ratio of 0.43.
Subgroup analyses showed that the treatment effect was consistent across multiple groups, divided by age, region, sensitivity to prior hormonal therapy, visceral metastasis, last therapy, last therapy setting, and prior chemotherapy.
Everolimus was also superior to placebo with respect to overall response rates (9.5% vs 0.4%) and clinical benefit (33.4 vs 18.0%).
Overall survival data is not yet mature; at the time of the interim analysis, 10.6% of patients in the everolimus arm had died versus 13.0% in the placebo arm.
Toxicity was consistent with previous trials of everolimus, with stomatitis, fatigue, dyspnea, anemia, and hyperglycemia being the most frequent grade 3/4 events. Quality of life did not differ significantly between the two treatment arms.
"Everolimus is the first agent to enhance the clinical benefit of hormonal therapy in refractory ER+ patients," Baselga concluded. "Our results could represent a paradigm shift in the management of patients with hormone-receptor-positive breast cancer."
The discussant, Fabrice André (Institut Gustave Roussy, Villejuif, France), congratulated the investigators on the trial, which he described as "the most important advance in breast cancer since trastuzumab."
He said that BOLERO-2 was methodologically robust, consistent with prior data, and clinically relevant. "The efficacy of everolimus is in the range of the most important recent advances in medical oncology," he noted, adding that this was particularly impressive since no molecular selection was used.
"Everolimus not only improves outcome but also opens new perspectives in the field of kinase inhibitors," he concluded.
By Jo Lyford