SAN FRANCISCO – In patients who had hormone receptor–positive, HER2-negative advanced breast cancer, everolimus plus exemestane was just as effective among women who had a recurrence during or within a year of adjuvant therapy.
The results were seen in a secondary, subgroup analysis of 137 patients in the BOLERO-2 (Breast Cancer Trials of Oral Everolimus 2) study. The subset that had recurrences during or within a year of adjuvant therapy comprised 19% of the patients in the study, and their outcomes were similar to the overall results of the trial, which support the use of everolimus plus exemestane as first-line therapy in postmenopausal patients with hormone receptor–positive advanced breast cancer that recurs after adjuvant therapy, Dr. Hope S. Rugo and her associates reported in a poster session at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
Dr. Hope Rugo
In the women who had a recurrence during or within 12 months of adjuvant therapy, everolimus plus exemestane improved median progression-free survival to 11.5 months, compared with 4.1 months with placebo plus exemestane.
The multicenter, double-blind BOLERO-2 study randomized 724 postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer that had recurred or progressed despite nonsteroidal aromatase inhibitor therapy. Patients received open-label exemestane plus blinded therapy with either placebo or everolimus, which inhibits the mammalian target of rapamycin (mTOR) signaling pathway. At 18 months of follow-up, patients in the exemestane-plus-everolimus group had a significantly longer median progression-free survival of 11 months as compared to 4 months for the control group (N. Engl. J. Med. 2012;366:520-529).
Similar efficacy was found in various analyses of subgroups in the study, including patients with visceral metastases, patients with bone-only metastases, and patients whose disease recurred after adjuvant therapy.
In the subgroup analysis of patients who entered the study after a recurrence during or within a year of adjuvant therapy, 100 patients received everolimus plus exemestane and 37 received placebo and exemestane. Almost all of the 137 patients had received nonsteroidal aromatase inhibitor therapy as their last therapy before entering the BOLERO-2 trial.
The median progression-free survival rates of 11.5 months with the everolimus combination and 4.1 months with the placebo combination were based on investigators’ local radiologic assessments. Central radiologic assessment by an independent radiology committee confirmed these results, finding that median progression-free survival reached 15.2 months in the everolimus group, compared with 4.2 months in the placebo group. Hazard ratios were 0.39 under the local assessment and 0.32 under the central assessment, reported Dr. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco.
Rates of the most common grade 3 or 4 adverse events seen in the everolimus-plus-exemestane group in the subset analysis – hyperglycemia in 8%, stomatitis in 4%, diarrhea in 4%, and fatigue in 3% – were similar to rates seen in the overall BOLERO-2 population and were within the known safety profile of everolimus. Some patients in the everolimus group (but not the placebo group) developed pneumonitis or interstitial lung disease, but these were mostly low grade and manageable by conventional strategies.
Baseline characteristics were well balanced in the randomized groups in the subset analysis.
The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
Novartis Pharmaceuticals, which markets everolimus, funded the study, and some of the investigators were company employees. Dr. Rugo reported having financial associations with Novartis, Merck, and Pfizer.
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