Afinitor® approved by European Commission to treat patients with the most common form of advanced breast cancer

NovartisThe European Commission has approved 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 postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor[1].

"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[1]. The randomized, double-blind, placebo-controlled, multi-center 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)[3]. The most common grade 3-4 adverse reactions (incidence >= 2%) were stomatitis, infections, hyperglycemia, fatigue, dyspnea, pneumonitis and diarrhea[3].

"By boosting the effectiveness of endocrine therapy, Afinitor significantly extends the time women with hormone receptor-positive advanced breast cancer live without tumor progression," said Jose Baselga, MD, PhD, Chief, Hematology/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."

Each year, an estimated 220,000 women globally will be diagnosed with HR+ advanced breast cancer[1],[4]. For these women, endocrine therapy remains the cornerstone of treatment, but most will eventually develop resistance to therapy[5]. This therapeutic resistance has been associated with overactivation of the PI3K/AKT/mTOR pathway[5]. Afinitor works to target the mTOR pathway in cells. mTOR is a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism[5].

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[6]. 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[7]. 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.

About Advanced Breast Cancer
Advanced breast cancer is comprised of metastatic breast cancer (stage IV) and locally advanced breast cancer (stage III)[8]. Metastatic breast cancer is the most serious form of the disease and occurs when the cancer has spread to other parts of the body, such as the bones or liver[8]. Locally advanced breast cancer occurs when the cancer has spread to lymph nodes and/or other tissue in the area of the breast, but not to distant sites in the body[8].

It is estimated that women with metastatic breast cancer have a life expectancy of approximately 18-36 months after diagnosis and median survival for women with stage III disease is less than five years[9],[10].

HR+ advanced breast cancer is characterized by hormone receptor-positive tumors, a group of cancers that express receptors for certain hormones such as estrogen and progesterone. Cancer cell growth can be driven by these hormones[8]. The presence of estrogen receptor (ER) and/or progesterone receptor (PgR) is one of the most important predictive and prognostic markers in human breast cancers, and is collectively referred to as hormone receptor-positive[8].

About Afinitor (everolimus)
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 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.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2011, the Group achieved net sales of USD 58.6 billion, while approximately USD 9.6 billion (USD 9.2 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Novartis Group companies employ approximately 126,000 full-time-equivalent associates and operate in more than 140 countries around the world.

* Known as Votubia® (everolimus) tablets for certain patients with SEGA associated with TSC in the EU and Switzerland.

1. Novartis Data on File.
2. Redmond C. Breast Cancer Hormone Therapy Options. Available at: Accessed April 27, 2012.
3. Piccart M et al. Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated Results of the BOLERO-2 Phase III Trial. Abstract #559. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL. 4. Buckley N, Isherwood A, Breast Cancer. Decision Resources. 2011.
5. Baselga J. Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer. New England Journal of Medicine. February 9, 2012.
6. European Medicines Agency. Summary of Opinion for Afinitor. June 21, 2012.
7. FDA Approval Announcement of Afinitor in Advanced HR+ Breast Cancer. July 20, 2012.
8. National Cancer Institute. What You Need to Know About Advanced Breast Cancer. Available at: Accessed on March 8, 2012.
9. Giordano S. Update on Locally Advanced Breast Cancer. The Oncologist, 2003.Buckley N, Isherwood A. Breast Cancer. Decision Resources, March 2011.
10. Eniua A, Palmierib F and Perez E. Weekly Administration of Docetaxel and Paclitaxel in Metastatic or Advanced Breast Cancer. The Oncologist, 2005.