Date: 2011-09-26
Type of information:
phase: 3
Announcement: results
Company: Novartis (Switzerland)
Product: Afinitor® (everolimus)
Action mechanism: Everolimus targets mTOR in cancer cells, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism. Resistance to hormonal therapy in breast cancer has been associated with over-activation of the mTOR pathway.
Disease: breast cancer
Therapeutic area: Cancer Oncology
Country: International study
Trial
details: BOLERO-2 (Breast cancer trials of OraL EveROlimus-2) examined the safety and efficacy of everolimus in combination with exemestane versus exemestane alone in postmenopausal women with ER+HER2- advanced breast cancer who recurred or progressed while on or following previous treatment with hormonal therapies, letrozole or anastrozole. This Phase III, randomized, double-blind, placebo-controlled, multicenter study was conducted at 189 sites worldwide and enrolled 724 patients. Patients who met the study criteria were randomized (2:1) to receive either everolimus 10 mg/day orally (n= 485), or placebo, plus oral exemestane 25 mg/day (n=239).
The primary endpoint was PFS based on local investigator radiology assessment. Additional analysis by an independent central radiology review committee showed everolimus extended PFS to 10.6 months compared to 4.1 months (hazard ratio 0.36; [95% CI: 0.27 to 0.47]; p<0.0001). Other endpoints include overall survival, overall response rate, safety, patient reported outcome, clinical benefit rate and changes in markers of bone metabolism. These data are being evaluated and will be submitted for publication or presentation in a peer-reviewed forum.
Latest
news: * On September 26, 2011, Novartis has announced that a pivotal Phase III study shows Afinitor® (everolimus) tablets plus exemestane, a hormonal therapy, more than doubled the time women lived without tumor growth (progression-free survival; PFS) and significantly reduced the risk of cancer progression by 57% versus exemestane alone in patients with advanced breast cancer. At a pre-planned analysis, the trial met its primary endpoint of PFS showing treatment with everolimus improved PFS to 6.9 months compared to 2.8 months (hazard ratio 0.43 [95% confidence interval (CI): 0.35 to 0.54]; p<0.0001) by local investigator assessment. This significant improvement was consistent across all subgroups including number of prior therapies, presence of visceral disease, bone metastases and prior use of chemotherapy. Data from BOLERO-2 support worldwide regulatory submissions, which are planned by the end of 2011. Additional data from BOLERO-2 will be presented at upcoming medical congresses this year.
* On July 5, 2011, an interim analysis of a pivotal Phase III study showed that Afinitor® (everolimus) tablets in combination with exemestane significantly extended progression-free survival (PFS), or time without tumor growth, when compared to placebo plus exemestane in women with advanced breast cancer. The trial was stopped early after interim results showed the primary endpoint of PFS was met. The study included postmenopausal women with ER+HER2- metastatic breast cancer whose disease has progressed, despite initial endocrine therapy. Results will be presented at an upcoming medical conference and worldwide regulatory submissions are being planned by the end of 2011.
