Table 1. Overview of novel therapeutic strategies under investigation for HER2-positive metastatic breast cancer.
| Agent | Type | Phase of developmenta | Clinical setting(s) |
|---|---|---|---|
| HER-targeted | |||
| Pertuzumab (Omnitarg) | Monoclonal antibody | III | First-line and relapsed; combination with trastuzumab+chemotherapy |
| T-DM1 | Antibody-drug conjugate | III | First-line and relapsed (after trastuzumab+taxane, after progression with ⩾2 prior HER2-targeted therapies); monotherapy, combination with pertuzumab |
| Lapatinib (Tykerb) | Reversible TKI | Approved | Relapsed (after anthracycline, taxane, and trastuzumab); combination with capecitabine |
| III | First-line; combination with letrozole (if hormone receptor positive) | ||
| First-line and relapsed; combination with chemotherapy or trastuzumab | |||
| Neratinib (HKI-272) | Irreversible TKI | III | First-line and relapsed (after trastuzumab±chemotherapy); combination with chemotherapy or trastuzumab |
| Afatinib (BIBW 2992) | Irreversible TKI | III | First- and second-line (after trastuzumab+chemotherapy, after trastuzumab and/or lapatinib progression); monotherapy, combination with chemotherapy |
| Anti-angiogenic | |||
| Bevacizumab (Avastin) | Monoclonal antibody | III | First-line; combination with chemotherapy and trastuzumab |
| Sunitinib (Sutent) | TKI | II | First- and second-line; combination with trastuzumab±chemotherapy |
| Pazopanib (Votrient) | TKI | II | First-line; combination with lapatinib |
| Other strategies | |||
| Tanespimycin (17-AAG) | Hsp90 inhibitor | IIb | First- and second-line (after trastuzumab progression); combination with trastuzumab |
| Retaspimycin (IPI-504) | Hsp90 inhibitor | II | Relapsed (after trastuzumab progression); combination with trastuzumab |
| AUY922 | Hsp90 inhibitor | I/II | Relapsed (after trastuzumab progression); monotherapy, combination with trastuzumab |
| BKM120 | Pan-PI3K inhibitor | I/II | Relapsed (after trastuzumab progression); combination with trastuzumab |
| BEZ-235 | PI3K/mTOR dual inhibitor | I/II | Relapsed (after trastuzumab progression); monotherapy, combination with trastuzumab; in PIK3CA and/or PTEN mutation-positive patients only |
| Everolimus (RAD001, afinitor) | mTOR inhibitor | III | First-line and relapsed (after trastuzumab resistance+taxane); combination with chemotherapy+trastuzumab |
| BMS-754807 | IGF-1R inhibitor | I/II | Relapsed (after trastuzumab failure); combination with trastuzumab |
| Cixutumumab (IMC-A12) | IGF-1R inhibitor | II | Relapsed (after trastuzumab and chemotherapy); combination with capecitabine/lapatinib |
Abbreviations: HER=human epidermal growth factor receptor; hsp90=heat shock protein 90; IGF-1R=insulin-like growth factor-1 receptor; mTOR=mammalian target of rapamycin; TKI=tyrosine kinase inhibitor; T-DM1=trastuzumab DM1.
a
Specific to breast cancer only, unless otherwise indicated.
b
Further clinical development has been halted.