Table 1.

Current options for targeting HER2 in metastatic HER2-positive IBC

Therapy	Evidence					Comments
	Clinical trial	Prior therapy	Arms	Results	End point
Lapatinib and capecitabine	NCT00078572 [11]	Anthracycline, taxane, and trastuzumab	Lapatinib and capecitabine	8.4 mo	PFS	Stable CNS metastases included
			Capecitabine	4.4 mo
Pertuzumab, trastuzumab, and taxane	CLEOPATRA (NCT00567190) [7]	None	Pertuzumab, trastuzumab, and docetaxel	56.5 mo	Median OS	First-line therapy
			Placebo, trastuzumab, and docetaxel	40.8 mo
Trastuzumab emtansine (T-DM1)	EMILIA (NCT00829166) [8]	Trastuzumab and taxane	Trastuzumab emtansine	30.9 mo	Median OS	Commonly used as second-line therapy
			Lapatinib and capecitabine	25.1 mo
	TH3RESA (NCT01419197) [9]	Trastuzumab, lapatinib, and taxane	Trastuzumab emtansine	22.7 mo	Median OS
			Physician's choice	15.8 mo
Trastuzumab deruxtecan (DS-8201)	DESTINY-Breast01 (NCT03248492) [10]	Trastuzumab emtansine	Trastuzumab deruxtecan	60.9%	ORR	Subgroup of trastuzumab emtansine immediately before − 64.3%
Neratinib and capecitabine	NALA (NCT01808573) [13]	At least 2 anti-HER2 therapies	Neratinib and capecitabine	8.8 mo	Mean PFS
			Lapatinib and capecitabine	6.6 mo
Tucatinib, capecitabine, and trastuzumab	HER2CLIMB (NCT02614794) [14, 17]	Trastuzumab, pertuzumab, and trastuzumab emtansine	Tucatinib, capecitabine, and trastuzumab	21.9 mo	Median OS	CNS metastases subgroup − 18.1 versus 12.0 mo
			Placebo, capecitabine, and trastuzumab	17.4 mo
Margetuximab and chemotherapy	SOPHIA (NCT02492711) [15]	At least 2 anti-HER2 therapies	Margetuximab and chemotherapy	5.8 mo	Median PFS	Presence of CD16A-158F allele may predict margetuximab benefit
			Trastuzumab and chemotherapy	4.9 mo

IBC, inflammatory breast cancer; CNS, central nervous system; HER2, human epidermal growth factor receptor 2; OS, overall survival; PFS, progression-free survival; ORR, overall response rate.