Novartis has received the European Commission approval for Afinitor (everolimus) tablets for the treatment of hormone receptor-positive (HR+), HER2/neu-negative (HER2-) advanced breast cancer (HR+ advanced breast cancer), in combination with exemestane, in post-menopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor.

“The approval of Afinitor is an important milestone marking the first major advance for women in the European Union with hormone receptor-positive advanced breast cancer since the introduction of aromatase inhibitors more than 15 years ago,” said Hervé Hoppenot, president, Novartis Oncology. "Treatment with Afinitor gives women a new option in the battle against this advanced form of breast cancer, where there remains a significant unmet need."

The approval was based on the phase III BOLERO-2 (Breast cancer trials of OraL EveROlimus-2) trial. The randomized, double-blind, placebo-controlled, multi-centre study of 724 patients found that treatment with Afinitor plus exemestane more than doubled median progression-free survival (PFS) to 7.8 months, compared to 3.2 months with exemestane alone (hazard ratio=0.45 [95% Cl: 0.38 to 0.54]; p<0.0001), by local investigator assessment[3]. An additional analysis based on an independent central radiology review showed Afinitor extended median PFS to 11.0 months compared to 4.1 months (hazard ratio=0.38 [95% CI: 0.31 to 0.48]; p<0.0001). The most common grade 3-4 adverse reactions (incidence >= 2%) were stomatitis, infections, hyperglycemia, fatigue, dyspnea, pneumonitis and diarrhoea.

“By boosting the effectiveness of endocrine therapy, Afinitor significantly extends the time women with hormone receptor-positive advanced breast cancer live without tumour progression,” said Jose Baselga, MD, PhD, chief, Haematology/Oncology, Massachusetts General Hospital and co-lead investigator of the BOLERO-2 trial. "Afinitor, the first mTOR inhibitor to be approved for this disease, has the potential to redefine the way this common form of advanced breast cancer is treated."

For women, endocrine therapy remains the cornerstone of treatment, but most will eventually develop resistance to therapy. This therapeutic resistance has been associated with overactivation of the PI3K/AKT/mTOR pathway. Afinitor works to target the mTOR pathway in cells. mTOR is a protein that acts as an important regulator of tumour cell division, blood vessel growth and cell metabolism.

The European Commission decision follows the positive opinion adopted by the Committee for Medicinal Products for Human Use on June 21, 2012 for Afinitor for the treatment of HR+ advanced breast cancer and applies to all 27 EU member states, plus Iceland and Norway. On July 20, 2012, the US Food and Drug Administration approved Afinitor in combination with exemestane in the HR+/HER2- population after failure of letrozole or anastrazole. Additional regulatory submissions for Afinitor in advanced breast cancer are under way worldwide. Afinitor is also being studied in HER2-positive breast cancer in two ongoing phase III trials.

Afinitor (everolimus) is approved in the European Union for the treatment of hormone receptor-positive (HR+), HER2/neu-negative (HER2-) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. In the United States, Afinitor is approved for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ breast cancer) in combination with exemestane after failure of treatment with letrozole or anastrozole.

Afinitor (everolimus) tablets is approved in more than 80 countries including the United States and throughout the European Union in the oncology settings of advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy, and in the United States and European Union for locally advanced, metastatic or unresectable progressive neuroendocrine tumours of pancreatic origin.

Everolimus is also available from Novartis for use in non-oncology patient populations under the brand names Afinitor or Votubia, Certican and Zortress and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.