On December 12, 2014 Novartis reported on results of the BOLERO-1 (Breast cancer trials of OraL EveROlimus-1) trial of Afinitor (everolimus) tablets in combination with trastuzumab (Herceptin*) and paclitaxel as a first-line treatment in women with human epidermal growth factor receptor-2 positive (HER2+) advanced breast cancer at the 2014 San Antonio Breast Cancer Symposium (SABCS) (Press release Novartis, DEC 12, 2014, View Source [SID:1234501181]).

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The trial was conducted in HER2+ advanced breast cancer patients, a population that represents approximately 20% of advanced breast cancers and differs from the hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer patients for whom Afinitor in combination with exemestane following a non-steroidal aromatase inhibitor is approved worldwide. The study did not meet the threshold of statistical significance for the primary objectives of progression-free survival (PFS) among women with HER2+ advanced breast cancer or the pre-defined hormone-receptor negative, human epidermal growth factor receptor-2 positive (HR-/HER2+) subgroup.

"For more than two years, Afinitor has positively impacted the HR positive treatment landscape as an important therapy for women living with advanced breast cancer," said Alessandro Riva, Global Head, Oncology Development and Medical Affairs, Novartis Oncology. "The results of this trial in HER2 positive support our research approach of investigating various treatment combinations targeting the PI3K/AKT/mTOR pathway in advanced breast cancer and we thank all of the researchers and patients who participated in the BOLERO-1 study."

The results of BOLERO-1, a Phase III, randomized, double-blind, placebo-controlled multicenter trial of 719 patients with HER2+ locally advanced or metastatic breast cancer, showed that the median PFS with everolimus plus trastuzumab and paclitaxel was 15.0 months versus 14.5 months with placebo plus trastuzumab and paclitaxel, a difference of 0.5 months (hazard ratio=0.89 [95% CI: 0.73 to 1.08]; p=0.1166).

In the HR- subgroup of women with HER2+ advanced breast cancer, a second primary objective, everolimus plus trastuzumab and paclitaxel treatment demonstrated benefit over the placebo arm prolonging median PFS by 7.2 months. The median PFS was 20.3 months with everolimus plus trastuzumab and paclitaxel and 13.1 months with placebo plus trastuzumab and paclitaxel. While this difference was clinically relevant, the results did not demonstrate statistical significance.

The combination of everolimus, trastuzumab and paclitaxel was generally well-tolerated. Adverse events were consistent with the known safety profile of everolimus with the most common all-grade adverse reactions (incidence >= 35%) being stomatitis, diarrhea, alopecia, rash, cough, pyrexia, neutropenia and fatigue. The most common Grade 3-4 adverse reactions (incidence >= 2%) were neutropenia, stomatitis, diarrhea, anemia, hypokalaemia, leukopenia, hyperglycemia, fatigue, pyrexia and dyspnea.

Afinitor is currently approved in more than 90 countries across the globe, including the countries of the European Union and the United States, to treat postmenopausal women with HR+/HER2- advanced breast cancer in combination with exemestane after recurrence or progression following a non-steroidal aromatase inhibitor. The specific indications vary by country. HR+/HER2- advanced breast cancer is the most common form of the disease. Approximately 70% of all invasive breast cancers are positive for HR expression at the time of diagnosis.