Table 1.
pCR rates in breast and nodes in neoadjuvant studies of nab-paclitaxel
| Author and year of study | Regimen | Phase | ER/PR status | HER2 status | Stage | ITT | pCR rate in populations of interest | Definition of pCR | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sequence | nab-P | Concurrent agents | n | pCR (%) | |||||||
| Veerapaneni 2008 [27] | nab-P + cape | 260 mg/m2 q3w (21-day cycle) | Cape 825 mg/m2 BID days 1–14 (21-day cycle) | II | Unselected | Unselected | II–IIIB | 14 | 7 | NR | No residual invasive carcinoma |
| Yardley 2010 [28] | nab-P + gem + E + peg | 175 mg/m2 q2w × 6 cycles | Gem 2000 mg/m2 q2w + E 50 mg/m2 q2w + peg 6 mg q2w × 6 cycles | II | Unselected | Unselected | I–IIIC | 123 | 20 | TNBC (n = 44), 27 % | ypT0 ypN0 |
| Robidoux 2010 [29] | nab-P → 4 cycles FEC (+ trastuzumab for HER2+) | 100 mg/m2 qw × 12 cycles | None | II | Unselected | Unselected | IIB-IIIB | 66 | In-breast: 29; breast-plus-node: 26 | pCR in breast only: TNBC (n = 18), 28 % HR+/HER2+ (n = 9), 44 % HR-/HER2+ (n = 10), 70 % |
In-breast ypT0 and breast-plus-node ypT0 ypN0 assessed |
| Yardley 2011 [52] | nab-P + carbo + trastuzumab + bevacizumab | 100 mg/m2 qw 3/4 (28-day cycles) × 6 cycles | Carbo AUC = 6 q3w + trastuzumab 2 mg/kg qw after 4 mg/kg in first week + bev 5 mg/kg qw (28-day cycles) × 6 cycles | II | Unselected | HER2+ | IIA–IIIC | 30 | 54 | ER+, 43 %; ER−, 66 % | ypT0 ypN0 |
| Khong 2011 [68] | nab-P + AC + peg | 100 mg/m2 qw 2/3 × 6 cycles | A 50 mg/m2 q3w + C 500 mg/m2 q3w + peg q3w × 6 cycles | I | Unselected | HER2− | II–III | 16 | NR | TNBC (n = 4), 100 % | ND |
| Li 2012 [69] | Docetaxel + AC | NA | NA | II | Unselected | Unselected | II–III | 18 | 17 | Treatment arms combined: Basal-like (n = 12), 25 % Luminal (n = 26), 8 % HER2+ (n = 15), 53 % |
RCB 0 |
| AC → nab-P + carbo | 100 mg/m2 qw 3/4 × 3 cycles | Carbo AUC = 2 qw 3/4 × 3 cycles | 26 | 8 | |||||||
| AC + trastuzumab → nab-P + carbo + trastuzumab | 100 mg/m2 qw 3/4 × 3 cycles | Carbo AUC = 2 qw 3/4 × 3 cycles | 28 | 46 | |||||||
| Kaklamani 2012 [31] | nab-P + lapatinib | 260 mg/m2 q3w (28-day cycles) × 4 cycles | Lapatinib 1000 mg qd × 12 weeks | Pilot | Unselected | HER2+ | I–III | 30 | ypT0 ypN0: 18; RCB 0: 21.7 |
NR | ypT0 ypN0 and RCB 0 |
| Sinclair 2012 [34] | Cohort 1: nab-P → nab-P + bevacizumab + carbo |
100 mg/m2 qw × 2 weeks → 100 mg/m2 qw × 12 weeks | Bevacizumab 15 mg/m2 q3w × 3 cycles + carbo AUC = 6 q3w × 4 cycles | II | Unselected | HER2− | IIA–IIIC | 31 | ypT0 ypN0/is: 11; RCB 0 + 1: 37 | TNBC (n = 11): ypT0 ypN0/is, 27 %; RCB 0 + 1, 55 % | ypT0 ypN0/is and RCB 0 + 1 |
| Cohort 2: bevacizumab → nab-P + bevacizumab + carbo → AC + bevacizumab |
100 mg/m2 qw × 12 weeks | Bevacizumab 15 mg/m2 q3w × 4 cycles + carbo AUC = 6 q3w × 4 cycles | 29 | ypT0 ypN0/is: 54; RCB 0 + 1: 64 | TNBC (n = 16): ypT0 ypN0/is, 81 %; RCB 0 + 1, 100 % | ||||||
| Snider 2013 [70] | nab-P + carbo + bevacizumab → AC + bevacizumab | 100 mg/m2 qw 3/4 (28-day cycle) × 4 cycles | Carbo AUC = 6 q4w + bevacizumab 10 mg/kg q2w (28-day cycle) × 4 cycles | NR | ER− PR− |
HER2− | I–III | 41 | ypT0, 61; ypT0 ypN0, 53 | NA | ypT0 and ypT0 ypN0 assessed |
| Masumoto 2014 [71] | nab-P q3w + carbo → FEC | NR | NR | II | Unselected | Unselected | Operable; stage not reported | 55 | 36.5 | HER2+ ,59 %; TNBC, 57 %; ER+ HER2−, 4 % | ypT0 ypN0 |
| Martin 2014 [37] | nab-P qw 3/4 | 150 mg/m2 qw 3/4 × 4 cycles | NA | II | ER+ PR unselected | HER2− | I–III | 83 | 24.1 % | RCB 0 + 1 24.7 % of treated population (20/81) | RCB 0 + 1 |
| Nahleh (S0800) 2014 [35] | Bevacizumab + nab-P → AC + peg-G | 100 mg/m2 qw × 12 weeks | Bevacizumab 10 mg/kg q2w × 12 weeks | II | Unselected | HER2− | IIB–IIIC | 215 | No bevacizumab, 21; bevacizumab, 36 (P = 0.021) | HR−: no bevacizumab, 28 % versus bevacizumab, 59 % (P = 0.014) HR+: no bevacizumab, 18 % versus bevacizumab, 25 % (P = 0.41) |
ypT0 ypN0 |
| nab-P → AC + peg-G | |||||||||||
| AC + peg-G → nab-P | |||||||||||
| Untch 2016 [39] | nab-P → EC | 125 mg/m2 qwa | – | III | Unselected | Unselected | Operable or inoperable; cT2-cT4a-d; cT1c and cN+ or pNSLN+ | 606 | ypT0 ypN0, 38; ypT0/is ypN0, 43; ypT0/is ypN0/+, 49 | HER2+: nab-P, 62 %; P, 54 % (P = 0.13) TNBC: nab-P, 48 %; P, 26 % (P < 0.001) |
Primary: ypT0 ypN0; secondary endpoints included ypT0/is ypN0 and ypT0/is ypN0/+, and ypN0 |
| Paclitaxel → EC | NA | 600 | ypT0 ypN0, 29; ypT0/is ypN0, 35; ypT0/is ypN0/+, 40 | ||||||||
| Mrozek 2010 [36] | nab-P + carbo + bevacizumab | 100 mg/m2 qw 3/4 × 6 cycles | Carbo AUC = 2 qw 3/4 + bevacizumab 10 mg/kg q2w × 6 cycles (no bevacizumab in 6th cycle) | II | Unselected | HER2− | II–III | 33 | 21 | TNBC, 55 % | ypT0 ypN0 |
| Zelnak 2012 [32] | nab-P → vin + trastuzumab | 260 mg/m2 q2w × 4 cycles | – | II | Unselected | HER2+ | I–III | 27 | 48.1 | ER+/PR+, 18.1 %; ER−/PR−, 68.8 % | ypT0 ypN0 |
| Connolly 2015 [72] | nab-P + carbo + placebo | 100 mg/m2 qw × 12 weeks | Carbo AUC = 2 qw + placebo 3 times per week × 12 weeks | II | Unselected | HER2− | Operable; T1cN1-3 or T2-4, any N, all M0 | 31 | 29 | TNBC: placebo, 58.3 % versus vorinostat, 41.7 % | ypT0 ypN0 |
| nab-P + carbo + vorinostat | 100 mg/m2 qw × 12 weeks | Carbo AUC = 2 qw + vorinostat 400 mg 3 times per week × 12 weeks | 31 | 25.8 | |||||||
| Huang 2015 [30] | nab-P + carbo | 125 mg/m2 qw × 4 cycles | Carbo AUC = 2 qw × 4 cycles | II | Unselected | Unselected | II–III | 30 | 26.7 | HER2+, 43.6 % versus 39.6 % for nab-P versus P (P = 0.769) | ypT0/is ypN0 |
| Paclitaxel + carbo | NA | Paclitaxel 80 mg/m2 qw + carbo AUC = 2 qw × 4 cycles | 90 | 25.6 | |||||||
| Shimada 2015 [40] | nab-P → EC | 260 mg/m2 q3w × 4 cycles | – | NA | Unselected | HER2− | II–III | 53 | 5.7 | NR | ypT0/is, ypNany |
| Tanaka 2015 [33] | EC or FEC → nab-P + trastuzumab | 260 mg/m2 q3w | – | II | Unselected | HER2+ | I–IIIA | 46 | 49 | ER+, 36 %; ER−, 71 % | ypT0/is ypN0 |
| Gluz 2015 [41] | nab-P + gem | 125 mg/m2 qw 2/3 | gem 1000 mg/m2 qw 2/3 | II | ER- PR- |
HER2− | I-IV | 182 | 28.7 | NA | ypT0/is ypN0 |
| nab-P + carbo | 125 mg/m2 qw 2/3 | Carbo AUC 2 day 1, 8 q3w | 154 | 45.9 | NA | ||||||
AC doxorubicin/cyclophosphamide, AUC area under the curve, bev bevacizumab, BID twice daily, carbo carboplatin, E epirubicin, EC epirubicin/cyclophosphamide, ER estrogen receptor, FEC fluorouracil/epirubicin/cyclophosphamide, gem gemcitabine, HER2 human epidermal growth factor receptor 2, ITT intent to treat, NA not applicable, nab-P nab-paclitaxel, NSLN non-sentinel lymph node, ND not defined, NR not reported, peg pegfilgrastim, pCR pathologic complete response, PR progesterone receptor, q3w every 3 weeks, qd once daily, qw once weekly, qw 3/4 for the first 3 of 4 weeks, RCB residual cancer burden, TNBC triple-negative breast cancer, vin vinorelbine, ypT0 ypN0 absence of invasive cancer and in situ cancer in the breast and axillary nodes, ypT0/is ypN0 absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ, ypT0/is absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement
aDose reduced from 150 mg/m2 qw (n = 229) to 125 mg/m2 qw (n = 377) after study amendment