Table 1 Characteristics of HER2-targeted tyrosine kinase inhibitors.
From: HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now
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 | ✓ | ✓ | ✗ | ✓ |
