ROCKVILLE, MarylandFDA has approved Bristol-Myers Squibb's Ixempra (ixabepilone) for treatment of resistant or refractory metastatic or locally advanced breast cancer. "We now have an important new option for patients with metastatic breast cancer who have rapidly progressed through currently approved chemotherapies," said Ixempra investigator Linda Vahdat, MD, of New York-Presbyterian Hospital/Weill Cornell Medical Center.
Ixempra, a semisynthetic analog of epothilone B that acts as a microtubule inhibitor, is indicated for use as a single agent in patients with advanced breast cancer who are no longer responding to anthracyclines, taxanes, and capecitabine (Xeloda), and in combination with capecitabine in patients with metastatic or locally advanced tumors that are refractory to anthracycline and taxane treatment, or in those patients whose cancer is taxane-resistant and further anthracycline therapy is contraindicated.
FDA's approval was based on the analyses of two multicenter trials that enrolled 878 patients.
A phase II single-arm trial evaluated Ixempra as monotherapy in 126 patients with advanced disease resistant to three prior therapies (an anthracycline, a taxane, and capecitabine). Among 113 evaluable patients, 12.4% had an objective partial response.
Treatment-related adverse events included peripheral neuropathy (62%; grade 3-4 14%) and fatigue/asthenia (56%, grade 3-4 13%). Grade 3-4 hematological events included neutropenia (54%) and leukopenia (49%).
A randomized phase III trial compared Ixempra/capecitabine to capecitabine alone. The investigators accrued 752 patients with prior resistance to anthracyclines and taxanes. Anthracycline resistance was defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic state. Taxane resistance was defined as progression while on therapy or within 12 months in the adjuvant setting or 3 months in the metastatic setting.
FDA found that Ixempra plus cape-citabine significantly improved progression-free survival (PFS), compared with capecitabine alone: 5.7 months vs 4.1 months (HR 0.69, P < .0001).