Table 1.

Key trials in targeted therapies for HER2+ breast cancer

Agent(s)	Treatment	Setting	Patient number	Results	References
Trastuzumab	Phase 3 trial of CT + TRAS vs CT alone	ABC; no prior CT for advanced disease	469	Significantly improved time to progression and OS	Slamon et al. [3]
Lapatinib	Phase 3 trial of LAP + CAP vs CAP alone	ABC with progression on TRAS + CT	324	Significantly improved time to progression	Geyer et al. [4]
	Phase 3 trial of LAP + LET vs LET alone	HR+, HER2+ ABC with no prior treatment for advanced disease	219	Significantly improved time to progression	Johnston et al. [5]
Lapatinib + trastuzumab	Phase 3 trial of LAP + TRAS vs LAP alone	MBC with progression on TRAS-based therapy	296	Significantly improved time to progression and OS	Blackwell et al. [6]
	Phase 3 trial of TRAS vs LAP vs TRAS + LAP (NeoALTTO)	Neoadjuvant therapy for HER2+ breast cancer	455	Significantly improved pCR for the LAP + TRAS arm	Baselga et al. [7]
	Phase 3 trial of TRAS vs LAP vs TRAS → LAP vs TRAS + LAP (ALTTO)	Initial adjuvant therapy for HER2+ EBC	8381	No significant difference in DFS across arms	Piccart-Gebhart et al. [8]
Pertuzumab + trastuzumab	Phase 3 trial of pertuzumab + TRAS + CT vs TRAS + CT (CLEOPATRA)	HER2+ ABC with no prior treatment for advanced disease	808	Significantly improved time to progression and OS	Swain et al. [9]
	Phase 3 trial of pertuzumab + TRAS + CT vs TRAS + CT (APHINITY)	Initial adjuvant therapy for HER2+ EBC	4805	Significantly improved iDFS	Von Minckwitz et al. [10]
	Phase 2 study of pertuzumab ± TRAS, TRAS + CT, or pertuzumab + CT (NeoSphere)	Treatment-naive early or locally advanced HER2+ BC	417	Dual targeting group had significantly improved complete response rate	Gianni et al. [11]
Trastuzumab emtansine (T-DM1)	Phase 3 study of T-DM1 vs LAP + CAP (EMILIA)	ABC with progression on TRAS + CT	991	T-DM1 significantly prolonged PFS and OS	Verma et al. [12]
	Phase 3 study of T-DM1 vs physician’s treatment of choice (TH3RESA)	ABC with previous treatment including TRAS, LAP, and a taxane	602	T-DM1 significantly prolonged OS	Krop et al. [13]
Neratinib	Phase 2 study of neratinib + paclitaxel vs TRAS + paclitaxel (NEfERT-T)	Previously untreated HER2+ MBC	479	Non-superior efficacy of neratinib vs TRAS	Awada et al. [14]
	Phase 3 trial of neratinib vs placebo as extended adjuvant therapy (ExteNET)	HER2+ EBC who completed (neo)adjuvant TRAS + CT	2840	Significantly reduced risk of clinically relevant BC relapse	Martin et al. [15]

ABC advanced breast cancer, BC breast cancer, CAP capecitabine, CT chemotherapy, EBC early breast cancer, DFS disease-free survival, HER2+ human epidermal growth factor receptor-2-positive, HR+ hormone receptor-positive, iDFS invasive disease-free survival, LAP lapatinib, LET letrozole, MBC metastatic breast cancer, OS overall survival, pCR pathological complete response, PFS progression-free survival, T-DM1 trastuzumab emtansine, TRAS trastuzumab