. Author manuscript; available in PMC: 2021 Apr 6.

Published in final edited form as: Nat Rev Clin Oncol. 2019 Dec 13;17(4):233–250. doi: 10.1038/s41571-019-0299-9

Table 1 |.

Currently approved HER2-targeted therapies for breast cancer and new agents in phase III trial

Drug	Mechanism of action	Administration route	Phase of development
*Monoclonal antibodies*
Trastuzumab	Binds to HER2 juxtamembrane domain IV	Intravenous or subcutaneous	Clinically approved in combination with chemotherapy for the adjuvant treatment of early stage HER2+ breast cancer and alone or in combination with chemotherapy for the treatment of advanced-stage disease
Pertuzumab	Binds to HER2 heterodimerization domain II	Intravenous	Clinically approved in combination with trastuzumab and chemotherapy for the treatment of advanced-stage HER2+ breast cancer and for the neoadjuvant and/or adjuvant treatment of early stage disease
Margetuximab	Fc-optimized HER2 monoclonal antibody with enhanced immune-effector function	Intravenous	Phase III SOPHIA trial: improved PFS with margetuximab and chemotherapy versus trastuzumab and chemotherapy in patients with pretreated metastatic HER2+ breast cancer¹⁶⁶
*Tyrosine kinase inhibitors*
Lapatinib	Reversible inhibitor of` EGFR (HER1) and HER2	Oral	Clinically approved in combination with capecitabine for the treatment of pretreated advanced-stage HER2+ breast cancer and in combination with letrozole for the first-line treatment of advanced-stage HER2+/HR+ disease
Neratinib	Irreversible pan-HER (HER1, 2, and 4) inhibitor	Oral	Clinically approved for extended adjuvant treatment of early stage HER2+ breast cancer after trastuzumab-based therapy
Tucatinib	Selective HER2 inhibitor	Oral	Phase III HER2CLIMB-02 (NCT03975647): T-DM1 ± tucatinib in patients with pretreated metastatic HER2+ breast cancers. Phase I trials revealed promising PFS and CNS response rates^43,167
Pyrotinib	Irreversible EGFR (HER1) and HER2 inhibitor	Oral	Phase III PHENIX trial: pyrotinib plus capecitabine significantly improved PFS vs placebo plus capecitabine (11.1 months vs 4.1 months; HR 0.18, 95% CI 0.13–0.26; P <0.001) in patients with metastatic HER2+ breast cancer previously treated with trastuzumab and a taxane¹⁶⁸
*Antibody–drug conjugates*
Trastuzumab emtansine (T-DM1)	Humanized monoclonal antibody trastuzumab covalently linked to the cytotoxic agent DM1	IV	Clinically approved for the treatment of metastatic HER2+ breast cancer and for the adjuvant treatment of residual disease after neoadjuvant treatment with trastuzumab and chemotherapy
Trastuzumab deruxtecan	A humanized anti-HER2 antibody, a cleavable peptide-based linker and potent topoisomerase I inhibitor	IV	Phase III DESTINY trial: trastuzumab deruxtecan vs T-DM1 in patients with advanced-stage HER2+ breast cancer previously treated with trastuzumab and a taxane¹⁶⁹
*Biosimilars*
Trastuzumab-dkst	Similar mechanism of action and efficacy to trastuzumab	IV	Clinically approved^a
Trastuzumab-pkrb (CT-P6)		IV	Clinically approved^a
Trastuzumab-dttb		IV	Clinically approved^a
Trastuzumab-qyyp		IV	Clinically approved^a
Trastuzumab-anns		IV	Clinically approved^a

CNS, Central Nervous System; PFS, progression-free survival.

For the same indications as originator trastuzumab.