Table 2.
Available results from the main trials in early and metastatic HER2−low breast cancer
| Drug | NCT | Ref | Phase | Overall BC pts (HER2−low pts) | Setting | Treatments | Main results |
|---|---|---|---|---|---|---|---|
| mAbs | |||||||
| Trastuzumab | NCT01275677 | Fehrenbacher L. et al. [22] | III | 3,270 (3,270) | Early, adjuvant | Adjuvant CT with or without trastuzumab | 5y DFS: 89.8% versus 89.2% HR 0.98; p = 0.85 |
| Pertuzumab | NCT02491892 | Gianni L. et al. [23] | II | 78 (74) | Advanced | Pertuzumab monotherapy | ORR: PR 2.5% (2 pt s) |
|
| |||||||
| ADCs | |||||||
| T_DXd | NCT02564900 | Modi S. etal. [46] | 54 (54) | Advanced | T-DXd monotherapy | ORR: 37% mDOR: 10.4 months mPFS: 11.1 months |
|
| NCT03734029 | Modi S. et al DESTINY-Breast04 [31] | III | 557 (557) | Advanced | T-DXd versus TPC | PFS in HR+: 10.1 versus 5.4 months HR0.51; p < 0.001 PFS in all: 9.9 versus 5.1 months HR0.50; p < 0.001 OS in HR+: 23.9 versus 17.5 months HR 0.64; p = 0.003 OS in all: 23.4 versus 16.8 months HR 0.64; p = 0.001 |
|
| NCT04420598 | Pérez-García et al DEBBRAH [47] | II | 21 (8) | Advanced, CNS | T-DXd monotherapy | ORR CNS: 46.2% | |
| NCT04132960 | Mosele et al. [33] | II | 179 (73) | Advanced | T-DXd monotherapy | ORR: 71 % in HER2−positive, 37.5% in HER2−low, and 30% in HER2 0 patients PFS: 11.1 in HER2−positive, 6.7 in HER2−low, and 4.2 months in HER2 0 | |
| Trastuzumab | NCT02277717 | Banerji U. et al. [34] | 99 (49) | Advanced | SYD985 monotherapy | ORR in HR+: 28% | |
| Duocarmazina | ORR in TNBC: 40% PFS in HR+: 4.1 month PFS in TNBC: 4.9 month | ||||||
| XMT-1522 | NCT02952729 | Hamilton et al. [48] | 19 (not available) Advanced | XMT-1522 in monotherapy | DCR: 83% | ||
|
| |||||||
| Combinations therapies | |||||||
| Nelipepimut-S | NCT01570036 | Hickerson et al. [37] | IIb | 275 (275) | Early, adjuvant | Nelipepimut-S + GM-CSF + trastuzumab versus trastuzumab + GM-CSF | 24-months DFS ITT population: 89.9% versus 83.8%, Hazard Ratio 0.62, CI 0.31–1.25 24-months DFS rate TNBC: 92.6% versus 70.2%, Hazard Ratio 0.26, CI: 0.08–0.81 |
| NCT01479244 | Mittendorf et al. PRESENT [38] | III | 758 (758) | Early, adjuvant | Nelipepimut-S + GM-CSF versus placebo + GM-CSF | 3-year DFS: 77.1 % versus 77.5% | |
| GP2 | NCT00524277 | Mittendorf et al. [49] | II | 180 (79) | Early, adjuvant | GP2 + GM-CSF versus GM-CSF alone | 5-year DFS: 88% versus 81% |
| AE37 | NCT00524277 | Mittendorf et al. [49] | II | 301 (154) | Early, adjuvant | AE37 + GM-CSF versus GM-CSF alone | DFS: 77.2% versus 65.7% |
| Nivolumab Zenocutuzumab |
NCT03523572 NCT03321981 |
Hamilton et al. [50] Pistilli et al. [42] |
Ib II | 54 (16) 50 (50) |
Advanced Advanced |
Nivolumab + T-DXd Zenocutuzumab (MCLA-128) + ET |
ORR37.5%in HER2 low DCR 75.0% in HER2 low mPFS 6.3 months in HER2 low CBR (CR + PR + SD at 24 weeks): 16.7% |
BC, breast cancer; BOR, best overall response; CBR, clinical benefit rate; CDK4/6i, cyclin-dependent kinase 4/6 inhibitors; CNS, central nervous system; DCR, disease control rate; DFS, disease free survival; ET, endocrine therapy; GM-CSF, granulocyte-macrophage colony-stimulating facto; HR, hazard ratio; ITT, intention to treat; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.