Patients with ER/PR/HER2-negative (
triple negative) breast cancer are not candidates for hormonal
therapy or HER2-targeted agents. Ongoing research is aimed at identifying and understanding the benefit of established and emerging
therapies in this disease setting. Triple-negative patients may achieve early responses to
anthracyclines and
taxanes, but novel strategies are also eagerly sought. The
epothilone B analog
ixabepilone acts to stabilize microtubules and demonstrates antitumor activity in recent
breast cancer studies. Herein, we have analyzed efficacy and safety data of
ixabepilone specifically for the treatment of women with triple-negative disease. A retrospective analysis was completed using activity and toxicity data in the triple-negative subsets from 5 phase II studies. In addition, a prospective pooled analysis of triple-negative patients from 2 phase III trials is also reviewed. Of 2,261 patients evaluated in these trials, 556 (24.5%) had triple-negative
tumors. In the neoadjuvant setting,
ixabepilone produced a
pathologic complete response rate in the breast of 26% in triple-negative patients (vs. 15% in the non-triple-negative population). In patients with metastatic
breast cancer whose pretreatment status ranged from no prior
therapy to progression on several classes of agents, overall response rates (ORR) in the phase II
ixabepilone monotherapy trials ranged from 6 to 55%, comparable to rates seen in patients with non-triple-negative
tumors. The combination of
ixabepilone and
capecitabine in the phase II study resulted in an ORR of 23% in triple-negative patients. A similar ORR (31%) was observed for a preplanned pooled analysis of triple-negative patients in the phase III trials of
ixabepilone plus
capecitabine. The median progression-free survival (PFS) was significantly longer for triple-negative patients treated with
ixabepilone plus
capecitabine (4.2 months) compared with treatment with
capecitabine alone (1.7 months). No increase in toxicity was noted in the triple-negative subgroup compared with other patients.
Ixabepilone shows notable antitumor activity in patients with
triple-negative breast cancer when used in a variety of settings. The addition of
ixabepilone to
capecitabine results in an approximately twofold increase in median PFS for triple-negative patients versus
capecitabine alone and responses to
ixabepilone in triple-negative disease are comparable to those seen in patients with non-triple-negative
tumors.