Advancements in the Treatment of Metastatic Breast Cancer (MBC): The Role of Ixabepilone

Table 1

Clinical efficacy of ixabepilone (ixa) as a monotherapy or in combination with a targeted agent and/or chemotherapy in the neoadjuvant and first-line breast cancer settings.

Ixabepilone alone
Reference	Trial design	Treatment duration	Patients	Dosing schedule	Efficacy
[54]	Phase 2, single arm	Up to 4 cycles	𝑁=161; median age: 55 years; treatment-naive	Per the PI*	pCR in the breast: ER–: 29%ER/PR-negative: 33% ER/PR/HER2-negative: 26%ER–/HER2+: 46.1%%)
[50]	Phase 2, single arm	Until disease progression or unacceptable toxicity for up to 18 cycles	𝑁=93; median age: 52 years; patients received a prior anthracycline-based regimen as adjuvant treatment	Initial dose: Ixa 50 mg/m^2 as a 1-hour infusion (𝑛=19); Amended dose: Ixa 50 mg/m^2 as a 3-hour infusion (𝑛=9) Final dose: per the PI* (𝑛=65)	ORR: 41.5% (95% CI, 29.4–54.4%)
Ixabepilone combination therapies
Ixabepilone + trastuzumab + carboplatin
Reference	Trial design	Treatment duration	Patients	Dosing schedule	Efficacy
[44]	Phase 2, single arm	Up to 6 cycles of chemotherapy; responding patients or those with SD received trastuzumab until PD or study discontinuation	𝑁=59; median age: 51 (all treated patients) 𝑁=39; median age: 54 (centrally confirmed HER2+ patients)	Ixa 15 mg/m^2 and carboplatin AUC = 2 IV on days 1, 8, and 15 every 28 days + weekly trastuzumab (4-mg/kg loading dose, then 2 mg/kg IV) during chemotherapy then 6 mg/kg IV every; 3 weeks	All treated patients ORR: 44%Centrally confirmed HER2+ patients ORR: 41%
Ixabepilone + capecitabine versus capecitabine alone
Reference	Trial design	Treatment duration	Patients	Dosing schedule	Efficacy
[39]	Pooled analysis from 2 phase 3, randomized, open-label trials	Until disease progression or unacceptable toxicity	𝑁=149 (ixa + capecitabine); 𝑁=144 (capecitabine)	Ixa (per the PI*) + oral capecitabine 2000 mg/m^2 on day 14 every 3 weeks versus capecitabine 2500 mg/m^2 alone on day 14 every 3 weeks	ORR: 46% versus 24% PFS: 5.6 versus 2.8 months (HR = 0.58 [95% CI, 0.45–0.76]; 𝑃<0.0001)
Ixabepilone + bevacizumab versus paclitaxel + bevacizumab
Reference	Trial design	Treatment duration	Patients	Dosing schedule	Efficacy
[41]	Phase 2, multi-arm	Until disease progression or unacceptable toxicity	[A]: ixa + bevacizumab, 𝑁=46; [B]: ixa+bevacizumab, 𝑁=45; [C]: paclitaxel + bevacizumab, 𝑁=32	[A]: Ixa 16 mg/m^2 on days 1, 8, and 15 every 28 days + bevacizumab 10 mg/kg IV every 2 weeks; [B] Ixa (per the PI*) + bevacizumab 15 mg/kg IV every 3 weeks; [C] paclitaxel 90 mg/m^2 IV every 2 weeks + bevacizumab 10 mg/kg IV every 2 weeks	ORR [A]: 48% (95% CI, 32.9–63.1%) [B]: 71% (95% CI, 55.7–83.6%) [C]: 63% (95% CI, 43.7–78.9%) Median PFS (months) [A]: 9.6 (95% CI, 6.1–11.7) [B]: 11.9 (95% CI, 8.7–14.7) [C]: 13.5 (95% CI, 10.0–18.2)

*The recommended dosage of ixabepilone is 40 mg/m² administered intravenously over 3 hours every 3 weeks. Doses for patients with body surface area greater than 2.2 m² should be calculated based on 2.2 m². AUC: area under curve; CI: confidence interval; ER: estrogen receptor; HER2: human epithelial receptor-2-positive; HR: hazard ratio; IV: intravenous; ORR: objective response rate; PD: progressive disease; PFS: progression-free survival; PI: prescribing information; PR: partial response; SD: stable disease.