FDA Approves Everolimus for Advanced Breast Cancer

Roxanne Nelson

July 20, 2012

July 20, 2012 — The US Food and Drug Administration (FDA) announced today that everolimus (Afinitor, Novartis) has been approved to be used with exemestane (Aromasin, Pfizer) to treat postmenopausal women with advanced hormone receptor (HR)-positive, HER2-negative breast cancer.

The drug combination is intended to be used in patients with recurrent or progressive disease after failure of treatment with either letrozole (Femara, Novartis) or anastrozole (Arimidex, AstraZeneca).

"This is the first approval from the class of drugs known as mTOR inhibitors for the treatment of postmenopausal women with advanced [HR-]positive breast cancer," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a statement. "Afinitor is another example of the value of continuing to study drugs in additional types of cancer after their initial approval."

This approval marks the fifth indication for everolimus. The drug has previously received FDA approval for:

  • patients with advanced renal cell carcinoma that has progressed after treatment with other cancer therapies,

  • adult patients with progressive advanced neuroendocrine tumors of pancreatic origin,

  • patients with renal angiomyolipoma and tuberous sclerosis complex (TSC) not requiring immediate surgery, and

  • adults and children with subependymal giant cell astrocytoma associated with TSC who require treatment but are not candidates for curative surgery.

The current approval was based on the results of the Breast Cancer Trials of Oral Everolimus 2 (BOLERO-2) trial, a randomized, double-blind, placebo-controlled, multicenter study that evaluated 724 postmenopausal women with advanced HR-positive breast cancer who experienced disease recurrence or progression after prior therapy with letrozole or anastrozole.

As previously reported by Medscape Medical News, the BOLERO-2 was halted early because of the benefit observed. "Everolimus is the most important advance in breast cancer since trastuzumab," said Fabrice Andr&eeacute;, MD, from the Institut Gustave Roussy, Paris, France, who acted as discussant when the results of preplanned interim analysis of the trial were reported at the 2011 European Multidisciplinary Cancer Congress (EMCC) in Stockholm, Sweden.

The study results showed that treatment with everolimus plus exemestane more than doubled median progression-free survival to 7.8 months compared with 3.2 months for those treated with exemestane alone (hazard ratio, 0.45; 95% confidence interval, 0.38 - 0.54; P < .0001) by local investigator assessment. An additional analysis that was based on an independent central radiology also showed that the combined treatment extended median progression-free survival to 11.0 months compared with 4.1 months (hazard ratio, 0.38; 95% confidence interval, 0.31 - 0.48; P < .0001) with exemestane alone.

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

Last month, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion for everolimus in the HR-positive/HER2-negative population. In addition, regulatory submissions are currently being reviewed by health authorities worldwide.

"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, in a company press statement. Dr. Hortobagyi is chair of Breast Medical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston and an investigator in the BOLERO-2 trial.

"This approval redefines the treatment and management of advanced [HR]-positive breast cancer, offering a critical new option for physicians and patients," he added.

Everolimus is also being studied in HER2-positive breast cancer in 2 ongoing phase 3 trials, according to the manufacturer.


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