Bristol-Myers Squibb Company announced new data from studies of Ixempra (ixabepilone) plus capecitabine compared to capectabine alone, including a pre-specified sub set analysis demonstrating a significant increase in progression free survival (PFS) in patients with triple negative breast cancer.

The study results - which are from a pooled analysis of approximately 2,000 patients enrolled in two phase III clinical trials of Ixempra (046 and 048) - were presented at the 2008 San Antonio Breast Cancer Symposium (SABCS). Patients studied were either resistant to or pretreated with anthracyclines and taxanes. In the pooled analysis of the subset of 443 patients with triple negative breast cancer, data show that IXEMPRA plus capecitabine (n = 191 patients) is the first combination regimen to demonstrate statistically significant (p<0.0001) PFS compared to capecitabine (n = 208 patients) alone.

Triple negative breast cancer patients are diagnosed based upon the lack of three "receptors" - estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2). Triple negative tumours are typically aggressive tumours that do not respond to hormonal treatment or HER2 agents and have a faster rate of relapse. Patients with triple negative breast cancer have a shorter overall survival after treatment with traditional chemotherapies.

"Patients with advanced, triple negative breast cancer have limited treatment options and a poor prognosis," said Hope S. Rugo, M.D., Clinical Professor of Medicine and Director, Breast Oncology Clinical Trials Program, University of California San Francisco Helen Diller Family Comprehensive Cancer Center. "For this reason, it is important to explore the potential of other current and developmental therapies to discover more and effective treatment options for patients with this specific type of breast cancer."

In the triple negative pooled subset analysis, patients who received IXEMPRA and capecitabine had an overall response rate (ORR) of 31 per cent compared to 15 per cent for patients who received capecitabine alone . The PFS of the combination group was a median of 4.2 months compared to a median of 1.7 months (Hazard Ratio 0.63, 95% CI: 0.52-0.77) for the capecitabine-treated group. Both results were statistically significant. Although improvement in overall survival was noted, the pooled analysis did not demonstrate statistical significance.

Ixempra (ixabepilone) in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 x ULN or bilirubin >1 x ULN due to increased risk of toxicity and neutropenia-related death. The most common adverse reactions (?20%) reported by patients receiving Ixempra were peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhoea, and musculoskeletal pain. The following additional reactions occurred in ?20% in combination treatment: palmar-plantar erythrodysesthesia (hand-foot) syndrome, anorexia, abdominal pain, nail disorder, and constipation. Drug-associated haematologic abnormalities (>40%) include neutropenia, leukopenia, anaemia, and thrombocytopenia.

In addition to the study in triple negative patients, other pooled data analyses from studies 046 and 048 were presented at SABCS, including data on patients with taxane resistance, patients who had relapsed 12 months or less after adjuvant treatment with an anthracycline and a taxane and symptomatic patients who had Karnofsky performance status of 70-80.

Ixempra, is an epothilone approved as monotherapy for the treatment of patients with metastatic or locally advanced breast cancer in patients whose tumours are resistant or refractory to anthracyclines, taxanes, and capecitabine. IXEMPRA is also approved in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline, and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Anthracycline resistance is defined as progression while on therapy or within six months in the adjuvant setting or three months in the metastatic setting. Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or four months in the metastatic setting.