Table 1:
Efficacy and safety of anti- ErbB family drugs (excluding HER2− selective therapies) in breast cancer
| Drug | Class | Target | Phase | Subtype/Setting | N | Combination Partners | Activity | Tox. of special Interest |
|---|---|---|---|---|---|---|---|---|
| Cetuximab | mAb | Amplified EGFR | II II II |
mTNBC [89] MBC [22] Early TNBC Neoadj setting[90] |
102 19 25 |
Alone Cet/Tax/carbo Cet/Docetaxel |
ORR: 6–16% pCR rate: 24% |
Rash ≥ G3: 3% |
| Panitumumab | mAb | Amplified EGFR | II | mTNBC[91] Early TNBC (neoadj) setting[92] |
71 60 |
Panitumumab/Carbo/Gem Panitumumab/FEC100→ docetaxel |
ORR:42% PFS: 4.4 mo pCR rate: 46.8% |
Skin tox ≥ G3: 43.3–70% |
| Gefinitib | TKI | Mutant EGFR | II | HR+/Her2+/− MBC[93] HR+/HER2− MBC (TAM-resistant)[94] HR+ HER2+/−MBC (TAM-naïve)[95] Early BC (neoadj) [96] Early HR+ BC (neoadj)[97] |
40 71 290 206 |
Monotherapy ANA + Gef or plac TAM + Gef/plac EP→ Gef/Plac ANA+Gef vs ANA |
ORR: 0% ORR: 22% vs 28% mPFS: 10.9 vs 8.8 pCR rate: 5% ki67 change 0–16w: mean 1.37 (p=.26) |
Diarrhea G≥3: 10–13% Rash: G≥3: 16.1–30% |
| Erlotinib | TKI | Mutant EGFR | II | MBC[23] | 69 | Monotherapy | ORR: 3% | Rash: G≥2: 6–13% |
| Afatinib | TKI | Mutant EGFR | II III |
HER2−MBC[26] HER2+ MBC[98] |
50 208 |
Monotherapy Afatinib+ Vino vs Trastuzumab+Vino |
ORR: 0% mPFS: 5.6 vs 5.5 mo |
Diarrhea G≥3:40% Diarrhea G≥3: 24% Rash: G≥3:11% |
| Pyrotinib | TKI | panErbB | III | HER2+ MBC[99] | 266 | Pyrotinib + Cape vs Lapatinib + Cape | mPFS: 12.5 vs 6.8 mo HR: 0.39 CI: 0.25–0.56 | Diarrhea G3: 31% |
| LJM716 | mAb | HER3 | I | HER2+ /PIK3CA mutant MBC[85] | 10 | LJM716 Trastuzumab and alpelisib | ORR: 1/21 (4.8%); CBR > 30 weeks: 4/21 | G ≥3 diarrhea (n = 6), hypokalemia (n = 3), abnormal liver enzymes (n = 3) |
| Lumretuzumab | mAb | HER3 | I I |
Highly pretreated HER3 amplified solid tumors [100] HER3 +, HER2-Low Breast Cancer [101] |
25 35 |
Pertuzumab + paclitaxel | CBR: 21.3% ORR: 38% - 55% (untreated pts) |
No DLT, diarrhea 46.8% G3 Diarrhea 50% |
| Patritumab deruxtecan | ADC | HER3 | I/II | HER3-high or low TNBC or HR+/HER2−[102] | 172 | HER3-high: ORR:10–30% HER3-low: 29–33% |
ILD: 5% |
Notes: TKI: tyrosine kinase inhibitor; N: number; Tax: ; MBC: metastatic breast cancer; BC: breast cancer; mTNBC: metastatic triple negative breast cancer; HR+: hormone receptor positive; mPFS: median progression free survival; ORR: overall response rate; ANA: anastrozole; TAM: tamoxifen; pCR: pathological complete response; CBR: clinical benefit rate; DLT: dose-limiting toxicity; Plac: placebo; G: grade; mo: months; EP: epirubicin and paclitaxel; vino: vinorelbine; neoadj: neoadjuvant: tox: toxicities; cape: capecitabine; ILD: interstitial lung disease; pts: patients; Lapa: lapatinib; Pyro: pyrotinib