Table 4.

Clinical trials of ixabepilone in drug-resistant metastatic breast cancer

Study	Population	Evaluable for efficacy/enrolled	Pretreatment characteristics	Activity
Ixabepilone monotherapy
Trial 009, phase II [88]	Resistant to taxane; prior treatment with anthracycline-based regimena	49/49	All had received ≥1 prior taxane-based regimen (31 % had ≥2 regimens); 98% had a taxane-containing regimen as their most recent MBC therapy, and 73% had progressed within 1 month of the last administered taxane dose	ORR 12%; 41 % stable disease Median DOR 10.4 months Median TTP 2.2 months (95% CI, 1.4 to 3.2 months) Median OS 7.9 months (95% CI, 6.1 to 14.5 months)
Trial 081, phase II [89]	Resistant to an anthracycline, a taxane, and capecitabine	113/126	77% with visceral disease in liver and/or lung; 88% had completed ≥2 prior chemotherapy regimens for MBC, 48% had ≥3 lines	ORR 11.5%; 50% stable disease Median DOR 5.7 months (95% CI, 4.4 to 7.3 months) Median PFS 3.1 months (95% CI, 2.7 to 4.2 months) Median OS 8.6 months (95% CI, 6.9 to 11.1 months)
Ixabepilone/capecitabine combination
Trial 031, phase II [90]	Anthracycline-pretreated or resistant and taxane-resistantb	50/62	72% had baseline visceral metastases, 43% had ≥2 prior chemotherapy regimens in the metastatic setting for MBC	ORR 30%c; 32% stable disease Median time to response 6 weeks (range, 5 to 14 weeks) Median DOR 6.9 months (95% CI, 4.3 to 9.7 months)
Trial 046, phase III [92]	Pretreated with or resistant to anthracyclines and resistant to taxanesd	737/752	65% had ≥3 metastatic disease sites; 48% had received ≥1 prior regimen for MBC; 85% had progressed on prior taxane therapy for metastatic disease	ORR 34.7% vs. 14.3% Median DOR 6.4 months vs. 5.6 months Median PFS 5.8 months vs. 4.2 months; hazard ratio = 0.75 (95% CI, 0.64 to 0.88)e

MBC, metastatic breast cancer; ORR, overall response rate; DOR, duration of response; TTP, time to progression (months); CI, confidence interval; OS, overall survival; PFS, progression-free survival. ^aPatients had progressed within 4 months of taxane therapy (6 months, if adjuvant therapy only) and had a taxane as their last chemotherapy regimen. ^bPatients were ineligible if they had received more than three prior chemotherapy regimens for metastatic disease. ^cAll responders had extensive metastatic disease at baseline. ^dResistance to anthracycline and taxane is defined as tumor progression during treatment or within 3 months of the last administered dose in the metastatic setting, or recurrence within 6 months in the neoadjuvant or adjuvant setting. This was subsequently revised to include recurrence within 4 months of the last administered dose in the metastatic setting or 12 months in an adjuvant setting. ^eP = 0.0003.