Table 1.
Select trials of neoadjuvant immune checkpoint inhibitors + chemotherapy in early-stage TNBC
| Trial | Stage | N+ (%) | ICI | Chemotherapy Backbone | Adjuvant Therapy | Results |
|---|---|---|---|---|---|---|
| Randomised Phase III | ||||||
|
KEYNOTE-522 N = 1174 |
cT1N1-2, cT2-4N0-2 |
51.7 | Pembro | Carbo + paclitaxel, then AC (non-dd) |
Pembro, 1 year total No cape allowed |
pCR in ITT 64.8% vs 51.2%, p <0.001 3-year EFS 84.5% vs 76.8%, HR 0.63, p < 0.001 |
|
IMpassion031 N = 333 |
cT2-4N0-3 | 34 | Atezo | Nab-paclitaxel, then ddAC |
Atezo, 1 year total Cape allowed for RD |
pCR in ITT 58% vs 41%, p = 0.0044 pCR in PD-L1+ 69% vs 49%, p = 0.021 EFS immature |
|
NeoTRIPaPDL1 N = 280 |
cT1N1-3, cT2-4dN0-3 |
88 | Atezo | Carbo + nab-paclitaxel | AC/EC/FEC |
pCR 48.6% vs 44.4%, p = 0.48 EFS immature |
| Randomised Phase II | ||||||
|
GeparNuevo N = 174 |
cT2-T4dN0-3 | 31.4 | Durva |
Window: 2 weeks durva alone pre-chemo Nab-paclitaxel, then ddAC |
No adjuvant therapy |
pCR 53.4% vs 44.2%, OR 1.45 3-year DDFS 91.4% vs 79.5% , p = 0.0148 3-year OS 95.1% vs 83.1%, HR 0.26, p = 0.007 |
|
I-SPY2 N = 69 |
cT2-4dN0-3 | 43 | Pembro | Paclitaxel, then AC (dd or non-dd) | Clinicians’ discretion | pCR 60% vs 22% in TNBC cohort |
|
NCI10013 N = 67 |
cT2-4Nany | NA | Atezo | Carbo + paclitaxel | ddAC | pCR: 55.6% vs 18.8%, p-value 0.018 |
| Single-arm Phase II | ||||||
|
NeoPACT N =117 |
Stage I-III | 39 | Pembro | Carbo + docetaxel | Clinician’s discretion |
pCR: 60% overall 2-year EFS 89% |
|
CHARIOT N = 34 |
Stage III ≥ 15mm RD after AC x 4 47% N+ |
- | Ipi + Nivo | Paclitaxel (AC received prior to randomization) | Nivo |
pCR 24.2% 12-month EFS 85% |
| Neo-N |
cT1cN1, cT2-4N0-1 |
- | Nivo |
Window: 2 weeks nivo alone pre- or post-chemo Carbo + paclitaxel |
Clinicians’ discretion | ongoing |
| Combination with PARP-i | ||||||
|
I-SPY2 N = 73 (21 TNBC, 52 HR-positive, HER2 negative) |
Stage II-III | 29 | Durva + olaparib | Paclitaxel, then AC (dd or non-dd) | No adjuvant therapy |
pCR 47% vs 27% in TNBC cohort pCR 14% vs 28% in ER+ cohort |
TNBC triple negative breast cancer, HR-positive hormone receptor positive, ICI immune checkpoint inhibitor, N+ node-positive, pembro pembrolizumab, atezo atezolizumab, durva durvalumab, nivo nivolumab, ipi ipilimumab, carbo carboplatin, AC doxorubicin and cyclophosphamide, EC epirubicin and cyclophosphamide, F 5-fluorouracil, cape capecitabine, PARP-i PARP inhibitor, dd dose-dense (2-weekly), non-dd non-dose-dense (3-weekly), pCR pathological complete response, EFS event-free survival, DDFS distant disease-free survival, OS overall survival, ITT intent to treat, RD residual disease, PD-L1 programmed death ligand-1, HR hazard ratio