San Antonio, TX—Updated results from the phase 3 Breast Cancer Trials of Oral Everolinmus (BOLERO-2) showed that adding everolimus to the treatment regimen with the aromatase inhibitor exemestane more than doubles the time to disease progression in patients with advanced estrogen receptor (ER)-positive breast cancer whose disease has become refractory to hormonal therapy. “The addition of everolimus in advanced breast cancer could represent a paradigm shift in the management of this patient population,” said lead investigator Gabriel Hortobagyi, MD, Chair of Breast Medical Oncology, the University of Texas, M.D. Anderson Cancer Center, Houston, at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. Nearly all ER-positive patients with advanced cancer will develop resistance to hormonal therapies. Resistance to hormonal therapy in breast cancer has been associated with over-activation of the mTOR pathway. Everolimus targets the mTOR pathway, interfering with tumor cell proliferation, angiogenesis, and cell metabolism. “Everolimus is the first treatment to significantly enhance the efficacy of hormonal therapy in this patient population, where this remains a significant unmet need,” Dr Hortobagyi noted. BOLERO Details The new findings represent an additional 5 months of follow-up from the data first presented at the European Multidisciplinary Cancer Congress in September 2011, which garnered much attention. The updated analysis presented in San Antonio showed that treatment with everolimus plus hormonal therapy more than doubled progressionfree survival (PFS), from 3.2 months with exemestane alone to 7.4 months, representing a highly significant 56% reduction (P <1 × 10-16)in the risk of progression. “While this analysis was done with local tumor assessment, another assessment by central independent review found even greater benefit, with PFS of 11.0 months versus 4.1 months, a 64% risk reduction (P <1 × 10-16),” Dr Hortobagyi reported. In remarking on the robustness of the findings at a media briefing, Dr Hortobagyi noted that the prolongation of progression far exceeded the investigators’ expectations. “The study demonstrated not the 26% reduction in progression, as we had expected, but a 56% reduction in progression events, with a P value for which I don’t have enough fingers to count.” Disease-free survival rates at 1 year were 31% in the combination arm versus 10% in the exemestane-alone arm. Side effects were consistent with those previously reported with everolimus. Themost common grade 3 or grade 4 adverse events were stomatitis, anemia, hyperglycemia, dyspnea, fatigue, and pneumonitis, all occurring in <10% of patients receiving the combination. The addition of everolimus did not impact the quality of life, according to the patients’ Global Health Scores. As of December 2011, deaths had occurred in 29.3% of the placebo arm and 23.1% of the everolimus arm. The manufacturer is planning a regulatory submission for everolimus based on the BOLERO-2 results.
