Health Canada Approves (Pr)AFINITOR* in Advanced Breast Cancer for Women Battling This Disease

• Approval represents a development for Canadian patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer since aromatase inhibitors were introduced almost 15 years ago¹
• In a landmark study of 724 patients randomized to receive either the combination of AFINITOR* plus exemestane or placebo plus exemestane, there was a statistically significant clinical benefit of AFINITOR*  plus exemestane by more than doubling median progression-free survival²
• AFINITOR*, the first mTOR inhibitor approved for HR+, HER2-negative advanced breast cancer, is given after the disease progresses following prior therapy with letrozole or anastrozole²

DORVAL, QC, Jan. 16, 2013 /CNW/ - Novartis Canada today announced that Health Canada has approved AFINITOR* (everolimus) tablets for the treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer in combination with exemestane after recurrence or progression following treatment with letrozole or anastrozole.³

"Everolimus is the first in a new class of treatment to overcome resistance to endocrine therapy," said Dr. Sunil Verma, Canadian Medical Oncologist. "The approval of everolimus has the potential to redefine the way we treat hormone receptor-positive advanced breast cancer, and offers physicians and patients a new therapeutic option where there remains a significant need."

In Canada, an estimated 22,700 women were diagnosed with breast cancer in 2012.⁴ Of those newly diagnosed patients, approximately 10 per cent will have locally advanced and/or metastatic disease and 20 to 85 per cent of patients, depending on the initial stage, tumour biology, and treatment strategy used, who are diagnosed with early breast cancer will later develop recurrent and/or metastatic disease.⁵ Advanced breast cancer is currently considered an incurable disease. It is estimated that women with metastatic breast cancer have a life expectancy of approximately 18-36 months after diagnosis,⁶ and median survival for women with stage III disease is less than five years.⁷

Diagnosed with metastatic breast cancer in 2012, Susan Cooper knows first-hand what it's like to live with the disease.

"Advanced breast cancer has changed the way I look at life. Time is so precious. I try to make the most of every day and not let my cancer stop me from doing the things I love to do, like spending time with my grandchildren," said Susan. "My hope is that new treatments will help others live longer without their cancer getting worse, while allowing them to enjoy the time they have left."

For women with HR+, HER2-negative advanced breast cancer, endocrine therapy remains the cornerstone of treatment, but most will eventually develop resistance to this therapy.² Approximately 50 per cent of HR+ breast cancer patients with metastatic disease do not respond to initial treatment with hormone therapy, and almost all initial responders develop resistance.⁸ This therapeutic resistance has been associated with overactivation of the PI3K/AKT/mTOR pathway.² AFINITOR* targets the mTOR pathway, which is dysregulated in the majority of human cancers. mTOR is a protein that plays a central role in the regulation of cell growth, proliferation and survival³.

"Women living with metastatic breast cancer have unique needs that differ from those living with primary disease. In addition to much-needed programs and services to support these women, access to new treatments is crucial in battling this incurable, yet treatable, form of breast cancer," said Cathy Ammendolea, Chair, Canadian Breast Cancer Network.

About Advanced Breast Cancer
Hormone receptor-positive, HER2-negative advanced breast cancer (HR+, HER2-negative advanced breast cancer) is comprised of metastatic breast cancer (stage IV) and locally advanced breast cancer (stage III).⁹ 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.⁹ 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.¹⁰

HR+ breast cancer is characterized by hormone receptor tumours, a group of cancers that express receptors for certain hormones, such as estrogen and progesterone. Cancer cell growth can be driven by these hormones.⁹ 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 (HR+).

About AFINITOR*
AFINITOR* tablets are approved in more than 80 countries, including Canada, for the treatment of well- or moderately differentiated neuroendocrine tumours of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease that has progressed within the last 12 months the treatment of patients with metastatic renal cell carcinoma (RCC) of clear cell morphology, after failure of initial treatment with either of the VEGF-receptor TKIs1 sunitinib or sorafenib. To date, approximately 45,500 patients have been treated with everolimus worldwide across other approved indications.

Health Canada approval of AFINITOR* in HR+, HER2-negative advanced breast cancer was based on a randomized, double-blind, multi-center Phase III study of AFINITOR* plus exemestane versus placebo plus exemestane in postmenopausal women with estrogen receptor-positive, HER2-neu/non-amplified breast cancer with recurrence or progression following therapy with letrozole or anastrozole.

In the landmark study called BOLERO-2 (Breast cancer trials of OraL EveROlimus-2), a total of 724 patients were randomized to receive either the combination of everolimus (10 mg daily) plus exemestane (25 mg daily) or placebo plus exemestane arm. This pivotal study demonstrated a statistically significant clinical benefit of everolimus plus exemestane over placebo plus exemestane by more than doubling median progression-free survival (PFS) (median: 7.36 months versus 3.19 months).³

The most common adverse events (incidence ≥ 30%) were stomatitis, infections, rash, fatigue, diarrhea and decreased appetite. The most common grade 3-4 adverse events (incidence ≥ 3%) were stomatitis, infections, fatigue, dyspnoea and pneumonitis.^2,3,11

To help patients access AFINITOR*, Novartis Pharmaceuticals Canada Inc. (Novartis Oncology) is offering a patient support program called AfiniTRAC^TM. The AfiniTRAC^TM program pursues coverage options for patients and may provide financial assistance, in some cases, for qualified patients. In addition, when registering into the program, patients will receive a Patient Starter Kit which includes a booklet on managing their disease and understanding the possible side effects associated with treatment, as well as sample products that can help with the management of treatment. For more information about this program, patients are encouraged to call the AfiniTRAC™ hotline at 1-888-6AFINITOR.
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*VEGF receptor TKIs = vascular endothelial growth factor receptor tyrosine kinase inhibitors

About Novartis Oncology
Novartis Oncology has advanced the treatment of patients with breast cancer across the disease continuum. In addition to developing medicines that are specifically aimed at breast cancer, Novartis is a leader in seeking to improve outcomes for cancer patients, having brought to market the first medical therapy for the treatment of patients with bone complications associated with advanced malignancies, ^PrAREDIA* (pamidronate disodium), more than 20 years ago.

Since then, Novartis Oncology has a proven track record of discovering and developing therapies that aim to change the way patients live with various types of cancer. The company's commitment to breast cancer patients is demonstrated by ^PrFEMARA* (letrozole) and ^PrZOMETA* (zoledronic acid).

For more than 20 years, Novartis Oncology has helped pave the way for significant advances in the treatment of patients with breast cancer. The company's research priorities are determined by patient need and disease understanding. Novartis Oncology's research strategy is to identify the structure of a tumour and the molecular pathways of the disease to develop targeted medicines that address the unmet medical needs of patients.

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis.

*AFINITOR, AREDIA, FEMARA, and ZOMETA are registered trademarks.

References
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¹ Redmond C. Breast Cancer Hormone Therapy Options. Available at: http://suite101.com/article/breast-cancer-hormone-therapy-options-a197304 Accessed April 27, 2012.
² Baselga J. Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer. New England Journal of Medicine. February 9, 2012.
³ AFINITOR* Product Monograph.
⁴ Canadian Cancer Society. Breast cancer statistics at a glance. Available at: http://www.cancer.ca/canada-wide/about%20cancer/cancer%20statistics/stats%20at%20a%20glance/breast%20cancer.aspx. Accessed June 4, 2012.
⁵ Bernard-Marty C.  Facts and Controversies in Systemic Treatment of Metastatic Breast Cancer. The Oncologist. 2004;9:617-632. Available at: http://theoncologist.alphamedpress.org/content/9/6/617.full. Accessed June 4, 2012.
⁶ Eniua A, Palmierib F and Perez E. Weekly Administration of Docetaxel and Paclitaxel in Metastatic or Advanced Breast Cancer. The Oncologist, 2005.
⁷ Giordano S. Update on Locally Advanced Breast Cancer. The Oncologist, 2003.
⁸ Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med. 2011;62:233-47.
⁹ National Cancer Institute. What You Need to Know About Advanced Breast Cancer. Available at: http://www.cancer.gov/cancertopics/wyntk/breast/WYNTK_breast.pdf. Accessed on March 8, 2012.
¹⁰ Hortobagyi, GN. Everolimus for postmenopausal women with advanced breast cancer: updated results of the BOLERO-2 phase III trial. SABCS 2011. November 8, 2011.
¹¹ Piccart, Martine. Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated Results of the BOLERO-2 Phase III Trial. Poster #559. American Society of Clinical Oncology Annual Meeting.

SOURCE: Novartis Pharmaceuticals Canada Inc.

For further information:

Celeste Brown
External Communications, Novartis Pharmaceuticals Canada Inc.
[phone] ext. 1033
[e-mail]

Amanda Federchuk
Consultant, GCI Group [phone]
[e-mail]