Novartis Lands FDA Approval for Afinitor in Advanced Breast Cancer

The tablets have been approved for treatment of postmenopausal women in combination with exemestane.

The US Food and Drug Administration (FDA) has approved 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."

According to a release, each year, an estimated 220,000 women globally will be diagnosed with advanced HR+ breast cancer, the most common form of the disease2,3. In the United States, nearly 40,000 people are expected to be newly diagnosed with advanced breast cancer this year alone4. Approximately 70 percent 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 percent Cl: 0.38 to 0.54]; p<0.0001) by local investigator assessment2. 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 percent CI: 0.31 to 0.48]; p<0.0001) with exemestane alone2. The most common adverse reactions (incidence greater than or equal to 30 percent) were stomatitis, infections, rash, fatigue, diarrhea and decreased appetite2. The most common grade 3-4 adverse reactions (incidence greater than or equal to 2 percent) 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 Herve 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 resistance5. Therapeutic resistance has been associated with overactivation of the PI3K/AKT/mTOR pathway5. 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 3. 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 population6. Additional regulatory submissions are being reviewed by health authorities worldwide.

About Advanced Breast Cancer
Advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ breast cancer) is comprised of metastatic breast cancer (stage IV) and locally advanced breast cancer (stage III)7. 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 liver7. 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.

It is estimated that women with metastatic breast cancer have a life expectancy of approximately 18-36 months after diagnosis8, and median survival for women with stage III disease is less than five years.

Advanced HR+ breast cancer is characterized by hormone receptor tumors, a group of cancers that express receptors for certain hormones, such as estrogen and progesterone. Cancer cell growth can be driven by these hormones7. 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.

Source: Novartis via ProQuest Information and Learning Co.

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