Table 2 Selected studies of single-agent and synergistic combination cytotoxic therapies in estrogen receptor-positive, endocrine-refractory, or triple-negative metastatic breast cancer

II

Epirubicin 135 vs. 90 vs. 60 vs. 40 mg/m² [31]

+/- endocrine or endocrine

RR: 37% (90 or 135)

TTP: 8.4 (90) vs. 4.4 months (40)^a

III

Doxorubicin 60 mg/m² every 3

weeks vs. liposomal doxorubicin 50 mg/m² every 3 weeks CAELYX [32]

+/- adjuvant anthracycline

PFS: 7.8 vs. 6.9 months

OS: 22 vs. 21 months

III

Doxorubicin 75 m/m² every 3

weeks vs. docetaxel 100 mg/m² every 3 weeks [30]

Prior alkylator

RR: 33% vs. 48%^a

TTP: 21 vs. 26 weeks

OS: 14 vs. 15 months

II

Docetaxel 40 mg/m² every week,

6 weeks, every 8 weeks [37]

1st/2nd line

RR: 41%

CBR: 59

II

Paclitaxel 80 mg/m² every week

Prior anthracycline +/− every 3 weeks taxane

RR: 22%

TTP: 4.7 months

OS: 12.8 months

II

Paclitaxel 250 mg/m² every 3

weeks vs. 175 mg/m² every 3 weeks [83]

1st/2nd line

RR: 32% vs. 21%

III

Docetaxel 100 mg/m² every 3 weeks vs. paclitaxel 175 mg/m² every 3 weeks [33]

1st/2nd line

TTP: 5.7 vs. 3.6 months^a

OS: 15.4 vs. 12.7 months^a

III

Nab-paclitaxel 260 mg/m² every 3 weeks vs. paclitaxel 175 mg/m² every 3 weeks [38]

Unlimited; no prior taxane in metastatic setting

RR: 33% vs. 19%^a

TTP: 23 vs. 16.9 weeks^a

OS: 60.5 vs. 55.7 weeks

II

Nab-paclitaxel 300 every

3 weeks or 100 every week or 150 mg/m² every week vs. docetaxel 100 mg/m²

every 3 weeks [39]

1st line

RR: 49% (150) vs. 45% (100) vs. 35% (d)

PFS: 13 (150) vs. 7.5 months (d)^a

III

Docetaxel 100 mg/m² every 3 weeks vs. capecitabine 1,250 mg/m² every 3 weeks [50]

1st/2nd line

RR: 30% vs. 42%^a

TTP: 6.1 vs. 4.2 months^a

OS: 14.5 vs.11.5 months^a

III

Paclitaxel 175 g/m² every 3

weeks vs. paclitaxel 175 g/m² every 3 weeks + gemcitabine 1,250 mg/m² D1 and D8 every 3 weeks [54]

1st line

RR: 41% vs. 26%^a

TTP: 6.14 vs. 3.98 months^a

OS: 18.6 vs. 15.8 months^a

II

Vinorelbine 35-30 mg/m²

every week [40]

2nd/3rd line; anthracycline +/- taxane

RR: 25%

TTF: 6 months

OS: 6 months

II

Ixabepilone 40 mg/m²

every 3 weeks [41]

1st line

RR: 42%

TTP: 4.8 months

OS: 22 months

II

Ixabepilone 40 mg/m²

every 3 weeks [45]

2nd line after taxane

RR: 12%

TTP: 2.2 months

OS: 7.9 months

II

Ixabepilone 40 mg/m²

every 3 weeks [44]

3rd/4th line; anthracycline, taxane, and capecitabine

RR: 12%

PFS: 3.1 months

II

Ixabepilone 6 mg/m² per day

days 1-5 every 3 weeks [43]

1st/2nd line

RR: 57%

TTP: 5.5 months

II

Eribulin 1.4 mg/m² every

week × 2 weeks every 3 weeks [47]

Median 4 prior

RR: 9%-14%

PFS: 2.6 months

OS: 9 months

III

Eribulin 1.4 mg/m² every

week × 2 weeks every 3 weeks vs. physician choice [48]

Median 4 prior

PFS: 3.7 vs. 2.2 months

OS: 13.1 vs. 10.6 months^a

II

Capecitabine 1,255 mg/m²

twice a day × 14 days every twice a day × 14 days every 3 weeks + docetaxel 75 mg/m² 3 weeks [49]

Unlimited

RR: 26%

OS: 12.2 months

II

Capecitabine 1,250 mg/m²

twice a day × 14 days

every 3 weeks vs.

1st/2nd line

RR: 37% vs. 35%

capecitabine 1,000 mg/m²

twice a day × 14 days

every 3 weeks [51]

TTP: 4 vs. 4 months

II

Capecitabine 1,255 mg/m² twice a

day × 14 days every 3 weeks vs. cyclophosphamide 600 mg/m² + methotrexate 40 mg/m² + 5-fluorouracil 600 mg/m²

every 3 weeks [84]

1st line

RR: 30% vs. 16%

TTP: 4.2 vs. 3 months

OS: 19.6 vs. 17.2 months

III

Capecitabine 1,250 mg/m² twice a

day × 14 days every 3 weeks vs.

3rd line

RR: 29% vs. 43%^a

ixabepilone 40 mg/m² every 3

weeks + capecitabine 1,000 mg/m² twice a day × 14 days

every 3 weeks [56]

PFS: 4.2 vs. 6.2 months^a

OS: 15.6 vs. 16.4 months

II

Gemcitabine 1,200 mg/m² every

week × 3 weeks every 4 weeks [52]

1st line

RR: 37%

TTP: 5.1 months

OS: 21.1 months

II

Gemcitabine 800-850 mg/m² every

week × 3 weeks every 4 weeks [85]

1st-4th line

RR: 20%-25%

OS: 11-11.5 months