Table 1. Different pivotal trials and rates of LVEF decline for non-trastuzumab HER2-directed agents.

PH - Perjeta (pertuzumab) + Herceptin (trastuzumab); TH - Taxotrene (docetaxel) + Herceptin (trastuzumab); TPH - Taxotere (docetaxel) + Perjeta (pertuzumab) + Herceptin (trastuzumab); HER2 - human epidermal growth factor receptor 2; LVEF - left ventricular ejection fraction

References	Trials	Number of patients	Population studied	Comparative arms	Rate of LVEF decline
Von Minkowitz et al. [54]	Pertuzumab (APHINITY)	4805	Patients with HER2-positive breast cancer (node-positive / high-risk node-negative)	PH	0.6%
				Placebo + trastuzumab	0.2%
Gianni et al. [59]	Pertuzumab (NEOSPHERE)	417	Patients with localized HER2-positive breast cancer	TH	0.9%
				TPH	2.8%
				PH	0.9%
				Docetaxel + pertuzumab	1.1%
Perez, et al. [60]	Lapatinib	3689	Patients with metastatic HER2-positive breast cancer	Lapatinib	1.6%
Geyer et al. [61]	Lapatinib	324	Patients with metastatic HER2-positive breast cancer	Lapatinib + capecitabine	0.7%
				Capecitabine	2.4%
Awada et al. [62]	Neratinib (NEFERT-T)	479	Patients with metastatic HER2-positive breast cancer	Neratinib + paclitaxel	1.3%
				Trastuzumab + paclitaxel	3.0%
Baselga et al. [63]	Pertuzumab (CLEOPATRA)	808	Patients with metastatic HER2-positive breast cancer	TPH	4.6%
				TH + placebo	7.4%