Table 2.
Main characteristics of the randomized controlled trials included in the present meta-analysis.
| Study | Study design | Primary end point | Secondary end points | Treatment arms | Patients, n |
|---|---|---|---|---|---|
| NCT00408408 (19) | phase III | ypT0/isN0 | ypT0/is pN0, safety, clinical complete responses | T→AC T→AC+Bev TC→AC TC→AC+Bev TG→AC TG→AC+Bev |
201 199 204 201 197 204 |
| NCT00528567 (20) | phase III | IDFS | OS, DFS, safety | CT CT+Bev |
1290 1301 |
| NCT00567554 (21) | phase III | ypT0/is ypN0 | OS, DFS, DDFS, safety | EC-T EC-T+Bev |
969 956 |
| NCT00773695 (22) | phase II | ypT0/is ypN0 | safety | FEC-T FEC-T+Bev |
66 66 |
| NCT00856492 (23) | phase II | ypT0/is ypN0 | OS, EFS, safety | nP-AC AC-nP nP+Bev-AC |
62 51 98 |
| NCT00861705 (24) | phase II | ypT0/isN0 | EFS, OS, safety | wP-ddAC wP-ddAC+Bev wPCarbo-ddAC wPCarbo-ddAC+Bev |
115 113 113 113 |
| NCT01093235 (25) | phase III | ypT0/is ypN0 | DFS, OS, safety | D-FEC Bev+D-FEC |
401 399 |
| NCT01142778 (26) | phase II | ypT0/is ypN0 | DFS, OS, DDFS, safety | T+trastuzumab T+trastuzumab+Bev |
25 48 |
| NCT01190345 (27) | phase II | ypT0/is ypN0 | DFS, OS, safety, RFS | FEC-T FEC-T+Bev |
25 50 |
| PMID: 24136883 (28) | phase III | ypT0 ypN0 | ypT0/TisypN0;ypT0/TisypN0/+ | EC-T EC-T+Bev |
340 323 |
T→AC: four cycles of docetaxel (100 mg per square meter of body-surface area, administered intravenously on day 1 of the cycle) every 3 weeks, followed by four cycles of doxorubicin–cyclophosphamide (60 mg and 600 mg per square meter, respectively, administered intravenously every 3 weeks) (docetaxel group) TC→AC: capecitabine (825 mg per square meter, administered orally twice a day on days 1 through 14) added to docetaxel (75 mg per square meter, administered intravenously on day 1), followed by doxorubicin–cyclophosphamide (docetaxel–cape cit abine group) TG→AC: gemcitabine (1000 mg per square meter, administered intravenously on days 1 and 8) added to docetaxel (75 mg per square meter, administered intravenously on day 1), followed by doxorubicin–cyclophosphamide (docetaxel–gemcitabine group. Bevacizumab (15 mg per kilogram of body weight, administered intravenously, every 3 weeks) with each of the first six cycles of chemotherapy and for 10 additional doses every 3 weeks postoperatively. EC-T: epirubicin (at a dose of 90 mg per square meter of body surface area) plus cyclophosphamide (at a dose of 600 mg per square meter), both administered on day 1, every 3 weeks for four cycles, followed by four cycles of docetaxel at a dose of 100 mg per square meter on day 1, every 3 weeks. Eight cycles of bevacizumab (at a dose of 15 mg per kilogram of body weight intravenously every 3 weeks starting on day 1 of the first epirubicin–cyclophosphamide cycle). FEC-T: 4 cycles of FEC100 (5-fluorouracil 600 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by docetaxel 100 mg/m2 every 3 weeks or 12 weekly infusions of paclitaxel 80 mg/m2. Bevacizumab was administered intravenously at a dose of 15 mg/kg every third week or 10 mg/kg every other week in patients receiving docetaxel or paclitaxel, respectively. nP+Bev-AC: (bevacizumab) received intravenous (IV) administration of nab-paclitaxel 100 mg/m2 IV weekly for 12 weeks (nP × 12) with IV bevacizumab 10 mg/kg every 2 weeks (six doses), followed by IV doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 with pegfilgrastim 6 mg subcutaneously every 2 weeks for six cycles (ddAC × 6). nP × 12 followed by ddAC × 6, and those randomized to Arm 3 received ddAC × 6 first followed by nP × 12, both without bevacizumab. Paclitaxel 80 mg/m2 once a week for 12 weeks (wP) and were randomly assigned to the control regimen, with addition of bevacizumab 10 mg/kg once every 2 weeks for 9 doses, carboplatin area under the curve 6 once every 3 weeks for four doses, or both, followed by dose-dense doxorubicin and cyclophosphamide (AC). D-FEC: docetaxel 100 mg/m2 once every 21 days for three cycles, followed by fluorouracil 500 mg/m2, epirubicin 100 mg/m2, with cyclophosphamide 500 mg/m2 once every 21 days for three cycles. Bevacizumab 15 mg/kg (Genentech, South San Francisco and Vacaville, CA, USA) was given every 3 weeks with the first four cycles of chemotherapy in the experimental group. T+trastuzumab: two cycles of neoadjuvant docetaxel (100 mg/m2) plus trastuzumab (8 mg/kg in cycle 1, and 6 mg/kg thereafter), both administered intravenously (i.v.) every 3 weeks (q3w). Bevacizumab (15 mg/kg i.v. q3w). FEC-T: four 21-day cycles of FEC100 IV infusions (5FU 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) on day 1 plus bevacizumab (15 mg/kg on day 1), then received four 21-day cycles of docetaxel (100 mg/m2 on day 1). Bevacizumab (15 mg/kg on day 1). EC-T: epirubicin (E,90mg/m2) plus cyclophosphamide (C,600mg/m2), both administered on day1, every 3 weeks for four cycles, followed by four cycles of docetaxel (D,100mg/m2) on day1, every 3 weeks. Eight cycles of bevacizumab (B,15mg/kgbodyweight) intravenously e very 3 weeks starting on day 1 of the first EC cycle. RFS,relapse-free survival; DFS, disease-free survival; EFS, event-free survival; OS, overall survival; iDFS, invasive DFS.