FDA has approved Bristol-Myers Squibb's Ixempra (ixabepilone) for treatment of resistant or refractory metastatic or locally advanced breast cancer.
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).
Results updated at ECCO 2007 showed progression-free survival of 5.8 months vs 4.2 months (P = .0003). Said investigator Jacek Jassem, MD, of the Medical University of Gdansk, Poland, "Epothilones work differently than other classes of chemotherapy and are less susceptible to known tumor resistance mechanisms. Therefore, we believe this new class, and ixabepilone in particular, may be an effective treatment option for some metastatic breast cancer patients."
Ixempra/capecitabine also significantly improved PFS in the poor-prognosis subgroup of HER2 patients who had failed trastuzumab (Herceptin) as well as athracyclines/taxanes, according to a presentation at the 2007 ASCO Breast Cancer Symposium (abstract 151).
"This suggests that ixabepilone may be a candidate to combine with HER2-targeting agents," said Guillermo Lerzo, MD, of Hospital de Oncologia Maria Curie, Ciudad de Buenos Aires, Argentina.
Two ongoing clinical trials are underway to determine if Ixempra significantly improves survival.
In the safety analysis, neuropathy was the most significant adverse nonhematological event, with grade 3-4 neuropathy seen in 21% of the combination patients vs 0% on capecitabine alone. Grade 3-4 neutropenia and leukopenia occurred in 68% and 57%, respectively, of the combination patients vs 11% and 6% of the capecitabine-alone patients.
Ixempra should not be taken by patients who have reacted adversely to drugs that contain Cremophor or its derivatives, or by those with baseline bone marrow suppression. Ixempra with capecitabine is also contraindicated in patients with moderate-to-severe liver problems.