FDA Approves Drug for Breast Cancer Resistant to First-Line Treatments

ROCKVILLE, Md., Oct. 17 -- Bristol-Myers Squibb said its metastatic breast cancer drug ixabepilone (Ixempra) has received FDA approval for treatment of women with metastatic or locally advanced treatment-resistant breast cancer.

The FDA approved the drug, which is a microtubule inhibitor belonging to a class of antineoplastic agents called the epothilones, for monotherapy in women whose tumors are resistant or refractory to anthracyclines, taxanes, and capcetabine.

It was also approved for use in combination with capcetabine for women whose cancers are anthracycline or taxane resistant or for women in whom further anthracycline therapy is contraindicated.

Linda Vahdat, M.D., of New York-Presbyterian Hospital/Weill Cornell Medical Center and an investigator in company-sponsored clinical trials of the drug, said the approval would provide a new treatment option for women, "who have rapidly progressed through currently approved chemotherapies."

The company said that FDA approval was based on review of data from two multi-center, international trials of ixabepilone alone or in combination with capecitabine.

In a single-arm phase II study of 126 women with metastatic or locally advanced breast cancer resistant to three prior therapies (anthracycline, taxane, and capcitabine), the objective partial response rate was 12.4%, the company said.

Treatment-related non-hematological adverse events included peripheral sensory neuropathy in 62% of patients, fatigue/asthenia in 56%, myalgia/arthralgia in 49%, alopecia in 48%, nausea in 42%, stomatitis/mucositis in 29%, vomiting in 29% and diarrhea in 22%.

Treatment-related hematological adverse events greater than or equal to 20% included neutropenia (Grade 3 or 4 in 54% of patients) and leukopenia (Grade 3 or 4 in 49%).

In a phase III combination therapy trial with 752 patients, ixabepilone plus capcitabine improved survival by about 6 weeks compared with controls (median survival 5.7 months versus 4.1 months (P<0.0001, Hazard ratio=0.69, 95% CI, 0.58-0.83).

Treatment-related non-hematological adverse event rates when ixabepilone was used in combination with capecitabine included peripheral sensory neuropathy (65%) hand-foot syndrome (64%), fatigue/asthenia 60%, nausea 53%, diarrheas 44%, vomiting 39%, myalgia/arthralgia 34%, anorexia 34%, stomatitis/mucositis 31%, alopecia 31%, and constipation 22%.

Hematological adverse events included 68% neutropenia and leucopenia 57%.

The company said the ixabepilone in combination with capecitabine is contraindicated for patients with elevated liver enzymes.

The drug is also contraindicated in patients with a known history of a severe (CTC Grade 3/4) hypersensitivity reaction to agents containing Cremophor EL or its derivatives such as polyoxyethylated castor oil, who have a baseline neutrophil count <1500 cells/mm³ or a platelet count <100,000 cells/mm³.

The company said in its statement that the drug would "be available within days."