Novartis has received the US Food and Drug Administration (FDA) approval for Afinitor (everolimus) tablets 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 is the first and only treatment that boosts the effectiveness of endocrine therapy, significantly extending the time women with advanced breast cancer live without tumor progression," said Gabriel Hortobagyi, MD, Chair of Breast Medical Oncology, University of Texas MD Anderson Cancer Center. "This approval redefines the treatment and management of advanced hormone receptor-positive breast cancer, offering a critical new option for physicians and patients."

Each year, an estimated 220,000 women globally will be diagnosed with advanced HR+ breast cancer, the most common form of the disease. In the United States, nearly 40,000 people are expected to be newly diagnosed with advanced breast cancer this year alone. Approximately 70 per cent of all invasive breast cancers are positive for HR expression at the time of diagnosis.

The approval was based on a randomized, double-blind, placebo-controlled, multi-center trial called BOLERO-2 (Breast cancer trials of OraL EveROlimus-2), which evaluated 724 postmenopausal women with advanced HR+ breast cancer with recurrence or progression following prior therapy with letrozole or anastrozole.

This pivotal phase III study 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[2]. An additional analysis based on an independent central radiology review showed Afinitor plus exemestane 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) with exemestane alone.

The most common adverse reactions (incidence >= 30%) were stomatitis, infections, rash, fatigue, diarrhea and decreased appetite. The most common grade 3-4 adverse reactions (incidence >= 2%) were stomatitis, infections, hyperglycemia, fatigue, dyspnea, pneumonitis and diarrhea.

"The approval of Afinitor in advanced breast cancer marks a very proud day for the breast cancer community and Novartis. We are bringing a highly-effective treatment to women and their physicians who are in need of new approaches in the battle against this disease," said Hervé Hoppenot, president, Novartis Oncology. "This milestone is a result of an extensive collaboration with researchers around the world who have helped study Afinitor in advanced breast cancer, as well as the more than 700 women who participated in the trial."

While endocrine therapy remains the cornerstone of treatment for these women, most will eventually develop treatment resistance. Therapeutic resistance has been associated with overactivation of the PI3K/AKT/mTOR pathway. Afinitor targets the mTOR pathway, which is hyperactivated in many types of cancer cells. mTOR is a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism.

Marking the fifth indication for Afinitor, this is the first FDA approval for an mTOR inhibitor in the treatment of advanced HR+ breast cancer in the United States. Afinitor is also being studied in HER2-positive breast cancer in two ongoing Phase III trials. On June 21, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Afinitor in the HR+/HER2-negative population. Additional regulatory submissions are being reviewed by health authorities worldwide.

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 tumors 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.