Table 1.
Characteristics of the included studies.
| Neoadjuvant treatment | Adjuvant treatment | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study | Phase | N | MF | Chemotherapy (wks) | Anti-HER2 therapy | Chemotherapy (wks) | Anti-HER2 therapy | Arms | LN+ patients (%) | HR+ patients (%) | Duration# (wks) | Outcomes | |
| Adjuvant setting | |||||||||||||
| ExteNET∗ | III | 2840 | 5.2 y | UNK | T or none | UNK | T + N | 1420 | 1085 (76) | 816 (57) | 52 | DFS, IDFS, OS, and safety | |
| (Martin1 2017a; Martin2 2017a; Chan 2016) | T | 1420 | 1084 (76) | 815 (57) | |||||||||
| ALTTO∗ | III | 8381 | 6.9 y | UNK | None | Design 1: chemotherapy × (12–18) Design 2: A × (9–12) + Taxane × 12 Design 2B: (Doc + Carb) × 18 |
T + Lb | 2093 | 1080 (52) | 1203 (57) | 52 | DFS, OS, and safety | |
| (Piccart-Gebhart 2016; Moreno-Aspitia1 2017b; Moreno-Aspitia2 2017b) | T⟶Lb | 2091 | 1078 (52) | 1205 (58) | T12⟶L34 | ||||||||
| T | 2097 | 1072 (51) | 1200 (57) | 52 | |||||||||
|
| |||||||||||||
| APHINITY (Von Minckwitz 2017) | III | 4805 | 3.8 y | None | None | FEC × (9–12) + Doc/Pal × 12; or AC/EC × (8–12) + Doc/Pal × 12; or (Doc + Carb)×18 | T + P | 2400 | 1503 (63) | 1536 (64) | 52 | IDFS, DFS, OS, and safety | |
| T | 2405 | 1502 (62) | 1546 (64) | ||||||||||
|
| |||||||||||||
| Neoadjuvant setting | |||||||||||||
| EORTC 10054 | IIb | 128 | NR | Doc × 9 + FEC × 9 | L + T | NR | T | 52 | 33 (64) | 25 (48) | 9 | pCR (breast + nodes), pCR (breast), response rates, and safety | |
| (Bonnefoi 2014) | T | 53 | 36 (68) | 27 (51) | |||||||||
|
| |||||||||||||
| CALGB 40601 | III | 295 | NR | wP × 16 | L + T | AC × (8–12) | T | 117 | NR | 69 (59) | 16 | pCR (breast + nodes) and safety | |
| (Carey 2016) | T | 118 | 70 (59) | ||||||||||
|
| |||||||||||||
| NeoALTTO∗ | III | 455 | 3.84 y | wP × 12w | L + T | FEC × 9 | T + L | 152 | UNK | 77 (51) | 52 | pCR (breast + nodes), pCR (breast), ORR, safety, DFS, EFS, and OS | |
| (Baselga 2012; de Azambuja 2014) | T | T | 149 | 75 (50) | |||||||||
|
| |||||||||||||
| CHER-LOB∗ | IIb | 121 | NR | wP × 12 + FEC × 12 | L + T | NR | T | 46 | NR | 28 (61) | 26 | pCR (breast + nodes) and clinical objective responses | |
| (Guarneri 2012; Guarneri 2015) | T | 36 | 21 (58) | ||||||||||
|
| |||||||||||||
| NeoSphere∗ | II | 417 | 5 y | D × 12 | T + P | FEC × 9 | T | 107 | 75 (70) | 50 (47) | 12 | pCR(breast) and pCR (breast + nodes) | |
| (Gianni 2012; Gianni 2016) | None | T + P | D × 12 <+ FEC × 9 | 107 | 75 (70) | 51 (48) | Clinical response rate, safety, PFS, and DFS | ||||||
| D × 12 | T | FEC×9 | 107 | 75 (70) | 50 (47) | ||||||||
|
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| LPT109096 | II | 100 | NR | FEC × 12 + wP × 12 | T + L | UNK | UNK | 33 | 20 (61) | 20 (61) | 26 | pCR (breast + nodes), clinical complete response (CCR), and safety | |
| (Holmes 2013) | T | 33 | 15 (45) | 15 (45) | |||||||||
|
| |||||||||||||
| NSABP B-41∗ | III | 519 | 5 y | AC × 12 + wP × 12 | T + L | None | T | 174 | 85 (49) | 108 (62) | 12 | pCR(breast), pCR (breast + nodes), clinical complete response, safety, and OS |
|
| (Robidoux 2013; Robidoux 2016) | T | 181 | 92 (51) | 122 (67) | |||||||||
MF: median follow-up; A: anthracycline; FEC: fluorouracil + epirubicin + cyclophosphamide; Doc: docetaxel; Carb: carboplatin; Pal: paclitaxel; wP: weekly paclitaxel; wk: week; HR+: hormone receptor positive; LN+: lymph node positive; T: trastuzumab; L: lapatinib; P: pertuzumab; N: neratinib; T + L: trastuzumab plus lapatinib; T ⟶ L: trastuzumab followed by lapatinib; NR: unreported; UNK: unknown. #Duration of dual anti-HER2 therapy.∗Studies with more than one publication. aIn the ExteNET trial (Martin 2017), lymph node- (LN-) positive patients were divided into two subgroups, 1–3 positive LN (Martin1 2017) and ≥4 positive LN (Martin2 2017), for the subgroup analysis of LN status. b In the ALTTO trial (Moreno-Aspitia 2017), there were two experimental groups (trastuzumab plus lapatinib group (Moreno-Aspitia1 2017) and trastuzumab followed by lapatinib group (Moreno-Aspitia2 2017).