Table 1.

Molecular and clinical characteristics and mechanisms of antitumor action of HER2-targeted drugs

	Trastuzumab	Pertuzumab	Lapatinib	Neratinib
Type of molecule	Humanized IgG1, binds to juxtamembrane domain IV	Humanized IgG1, binds to heterodimerization domain II	Reversible, ATP-competitive, small molecule TKI	Irreversible, covalent, small molecule TKI
Administration, half-life	Intravenous, weeks	Intravenous, weeks	Oral, 24 h	Oral, ∼16 h
Cell surface HER2 levels	Reduces	No change	Increases	May increase
Receptor dimers	Inhibits HER2 homodimers and ligand-independent HER2–HER3 dimers	Inhibits ligand-induced HER2-containing heterodimers	May increase cell surface dimers	May increase cell surface dimers
Downstream signaling	Weak inhibitor	Weak inhibitor	Potent inhibitor	Potent inhibitor
HER2 ectodomain cleavage	Inhibits	Does not inhibit	No effect	No effect
Inhibits p95HER2	No	No	Yes	Yes
ADCC*	Yes	Yes	No	No
Exon 20 insertion and gatekeeper mutation	Inactive	Probably inactive	Inactive	Active
Cardiotoxicity	Rare	No	Rare	Rare
Diarrhea	Rare	Dose-limiting toxicity	Dose-limiting toxicity	Dose-limiting toxicity

^*antibody-dependent cell mediated cytotoxicity.