Table 1.
Characteristics of HER2-targeted tyrosine kinase inhibitors.
| Lapatinib50 | Neratinib88 | Pyrotinib19 | Tucatinib69 | |
|---|---|---|---|---|
| Inhibition | Reversible | Irreversible | Irreversible | Reversible |
| Target(s) | EGFR (HER1), HER2 (ErbB2) | EGFR (HER1), HER2 (ErbB2), HER4 | EGFR (HER1), HER2 (ErbB2), HER4 | HER2 (ErbB2) » EGFR (HER1) |
| Absorption | Variable (take 1 h before meals) | Increased by 70–120% by high fat meals (>50%) | Variable | Variable |
| Metabolism | Hepatic, via CYP3A4 and 3A5 > C19 and 2C8 | Hepatic, via CYP3A4 | Hepatic, via CYP3A4 | Hepatic, via CYP2C8 > 3A4 |
| IC50 |
EGFR 11 nM HER2 9 nM |
EGFR 92 nM HER2 59 nM |
EGFR 5.6 nM HER2 8.1 nM |
EGFR 449 nM HER2 6.9 nM |
| Excretion | Feces > urine | Feces » >urine | Feces | Feces » urine |
| Recommended dose | 1250 mg PO daily with capecitabine; 1500 mg PO daily with letrozole | 240 mg PO daily | 400 mg PO daily | 300 mg PO twice daily |
| US FDA approval in the adjuvant setting | ✗ | ✓ | ✗ | ✗ |
| US FDA approval in the metastatic setting | ✓ | ✓ | ✗ | ✓ |
IC50 half maximal inhibitory concentration, nM nanomole, EGFR epidermal growth factor receptor, mg milligrams, PO oral administration, US FDA United States Food and Drug Administration.