Table 2.
Summary of key efficacy measures across the clinical studies with ixabepilone in breast cancer.
| Phase | Patients, n | Population | Treatment | Efficacy | Study (year) | Ref |
|---|---|---|---|---|---|---|
| Ixabepilone monotherapy | ||||||
| II | 65 | Patients with mBC previously treated with adjuvant anthracycline | Ixabepilone 40 mg/m2 IV Q3W | ORR: 41.5% (95% CI, 29.4-54.4%); mTTP: 4.8 mo; mOS: 22.0 mo | Roché et al. | (25) |
| II | 126 | Patients with mBC who progressed during treatment with an anthracycline, taxane, and capecitabine | Ixabepilone 40 mg/m2 IV Q3W | ORR (IRF): 11.5% (95% CI, 6.3-18.9%), ORR (INV): 18.3%; mPFS: 3.1 mo; mOS: 8.6 mo; mDoR: 5.7 mo | Perez et al. | (19) |
| II | 49 | Patients with mBC who progressed during or within 4 mo of taxane therapy | Ixabepilone 40 mg/m2 or 50 mg/m2 IV Q3W | ORR (INV): 12% (95% CI, 4.7-26.5%); mDoR: 10.4 mo; mTTP: 2.2 mo; mOS: 7.9 mo | Thomas et al. | (26) |
| II | 52 | Patients with mBC resistant to taxanes and previously treated with anthracyclines | Ixabepilone 40 mg/m2 IV Q3W | ORR (IRF): 11.5% (95% CI 4.4-23.4%); mDoR: 3.6 mo; mTTP: 2.8 mo; mOS: 12.4 mo | Aogi et al. | (27) |
| Ixabepilone in combination with capecitabine | ||||||
| II | 103 | Patients with HER2-negative disease | Ixabepilone 20 mg/m2 IV + carboplatin (area under the curve 2.5) IV on days 1 and 8 of a 21-day cycle | ORR: 30.4% in TNBC and 34% in hormone receptor–positive HER2-negative disease; mPFS: 7.6 mo in TNBC and 7.6 mo in hormone receptor–positive HER2-negative disease; mOS: 12.5 mo in TNBC and 17.9 mo in hormone receptor–positive HER2-negative disease | Osborne et al. | (28) |
| III | 752 | Patients with locally advanced BC or mBC previously treated with or resistant to anthracyclines and resistant to taxanes | Ixabepilone 40 mg/m2 IV Q3W + capecitabine 2000 mg/m2 on days 1-14 of a 21-day cycle | mPFS: 5.8 mo (95% CI, 5.45-6.97) vs 4.2 mo (95% CI, 3.81-4.50; HR, 0.75; P=0.0003); ORR (IRF): 35% vs 14% (OR, 3.2; P<0.0001); mDoR: 6.4 mo vs 5.6 mo; mOS: 12.9 mo vs 11.1 mo | Thomas et al.; Hortobagyi et al. | (20, 21) |
| III | 1221 | Women with locally advanced BC or mBC previously treated with anthracyclines and taxanes | Ixabepilone 40 mg/m2 IV Q3W + capecitabine 2000 mg/m2 on days 1-14 of a 21-day cycle | Unadjusted mOS: 16.4 mo vs 15.6 mo (HR, 0.9; P=0.1162); prespecified adjusted Cox regression of mOS: HR, 0.85; 95% CI, 0.75 to 0.98; P=0.0231) mPFS: 6.24 mo vs 4.4 mo (HR, 0.79; P=0.0005); ORR (INV): 43% vs 29% (P<0.0001); DoR: 6.1 mo vs 6.3 mo | Sparano et al. | (22) |
| Meta-analysis | 2637 (OS) | OS: 3 studies (CA163-046, CA163-068; pooled dataset) | Ixabepilone 40 mg/m2 IV Q3W + capecitabine 2000 mg/m2 on days 1-14 of a 21-day cycle | OS HR, 0.91 (95% CI, 0.84-0.99) | Li et al. | (29) |
| PFS HR, 0.79 (95% CI, 0.74-0.85) | ||||||
| 3387 (PFS, ORR) | PFS, ORR: 4 studies (CA163-046, CA163-068; pooled dataset [<65 y and ≥65 y]) | ORR RR, 1.77 (95% CI, 1.45-2.15) | ||||
| Ixabepilone as adjuvant treatment | ||||||
| III | 762 | Patients with resectable, non-metastatic, poor-prognosis BC | 3x FEC100 Q3W + 3x ixabepilone 40 mg/m2 IV Q3W, or 3x FEC100 Q3W + 3x docetaxel 100 mg/m2 Q3W | 5-y DFS rate: 83% (95% CI, 79-87%) vs 79% (95% CI, 75-83%; HR, 0.80; P=0.175); 5-y OS rate: 88% vs 87% (HR, 0.97; P=0.897) | Campone et al. | (24) |
| III | 614 | Patients with operable, previously untreated TNBC | 4x doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 Q3W, followed by 4x ixabepilone 40 mg/m2 Q3W, or 12x paclitaxel 80 mg/m2 every week | 3-y DFS rate: 88.6% vs 88.8% (not significant); 5-y DFS rate: 87.1% vs 84.7% (not significant); 3-y OS rate: 92.4% vs 93.8% (not significant); 5-y OS rate: 89.7% vs 89.6% (not significant) | Yardley et al. | (23) |
| Subset analyses of special patient populations | ||||||
| Pooled phase III | 1973 | Participants with KPS 70%-80% and KPS 90%-100% in 2 phase III trials | Ixabepilone 40 mg/m2 IV Q3W in combination + capecitabine 2000 mg/m2 on days 1-14 of a 21-day cycle | KPS 70%-80%: mPFS: 4.6 mo (95% CI, 4.2-5.6) vs 3.1 mo (95% CI, 2.7-3.9; HR, 0.76; P=0.0021); mOS: 12.3 mo vs 9.5 mo (HR, 0.75; P=0.0015) KPS 90%-100%: mPFS: 6.0 (95% CI, 5.6-6.6) vs 4.4 (95% CI, 4.2-5.3; HR, 0.82; P=0.0009); mOS: 16.7 mo vs 16.2 mo (P=0.8111) | Roché et al. | (30) |
| Pooled phase III | 293 | Participants with PARR disease in 2 phase III trials | Ixabepilone 40 mg/m2 IV Q3W in combination + capecitabine 2000 mg/m2 on days 1-14 of a 21-day cycle | PARR: mPFS: 5.6 mo (95% CI, 4.6-6.9) vs 2.8 (95% CI, 2.2-3.7; HR, 0.58; P<0.0001); mOS: 15.1 mo vs 12.5 mo (HR, 0.84; P<0.2081) | Jassem et al. | (31) |
| Pooled phase III | 251 (≥65 y) 1721 (<65 y) | Participants aged <65 y and ≥65 y in 2 phase III trials | Ixabepilone 40 mg/m2 IV Q3W in combination + capecitabine 2000 mg/m2 on days 1-14 of a 21-day cycle | Age ≥65 y: mPFS: 5.5 mo vs 3.9 mo (HR, 0.77; 95% CI, 0.59-1.02); mOS 13.9 mo vs 12.2 mo (HR, 1.07; 95% CI, 0.81-1.40) Age <65 y: mPFS 5.6 mo vs 4.2 mo (HR, 0.81; 95% CI, 0.73-0.90); mOS: 14.7 mo vs 13.9 mo (HR, 0.90; 95% CI, 0.81-1.01) | Vahdat et al. | (32) |
| Pooled phase III | 443 | Participants with TNBC in 2 phase III trials | Ixabepilone 40 mg/m2 IV Q3W in combination + capecitabine 2000 mg/m2 on days 1-14 of a 21-day cycle | TNBC: mPFS: 4.2 mo (95% CI, 3.6-4.4) vs 1.7 mo (95% CI, 1.5-2.4; HR, 0.64; P<0.0001); mOS 10.4 mo vs 9.0 mo (HR, 0.88; P=0.1802) | Rugo et al. | (33) |
BC, breast cancer; CI, confidence interval; DFS, disease-free survival; DoR, duration of response; FEC, 5-FU+epirubicin+cyclophosphamide; HER2, human epidermal growth factor receptor; HR, hazard ratio; INV, investigator-assessed; IRF, independent radiology facility or committee; IV, intravenous; KPS, Karnofsky Performance Status; mBC, metastatic breast cancer; mDoR, median DoR; mo, month; mOS, median OS; mPFS, median PFS; mTTP, median time to progression; OR, odds ratio; ORR, objective response rate; OS, overall survival; PARR, post-adjuvant rapidly relapsing; PFS, progression-free survival; Q3W, every 3 weeks; TNBC, triple-negative breast cancer; y, year.