. 2022 Sep 1;5(4):873–881. doi: 10.20517/cdr.2022.48

Table 1.

HER2 alterations detected following neratinib-containing regimens in clinical trials of HER2-mutant MBC (compiled from the works of Ma et al.^[7], Ma et al.^[8], and Smyth et al.^[9])

Trial	Regimen	*HER2* mutations detected at baseline	Best response	Acquired HER2 alterations
MutHER
	N	L755S, P761del	PR	R678Q, V697L
	N + F	G778_P780dup	PR	D808H^a, T798I^b, I767M
	N + F	S310F	PR	L755S, D769Y, G776V, T798I^b, L841V
	N + F	G778_P780dup	PR	S310Y, S310F, I767M, T798I^b
	N	L869R; amplification	SD	D1011D^c
	N	L869R, D769Y	SD	S310F, I767M, T862A, T798I^b
	N + F	V777L	SD	S310F
	N + F	L755S	SD*	S310F
SUMMIT
	N + F	S310F	CR	L785F^b^,^d
	N + F	G778_P780dup	PR	I767M, S310Y, amplification^d
	N + F	L869R	PR	S310Y, D769Y, L755S, T798I^b
	N + F	V697L	PR	Amplified mutant allele^d
	N + F	V777L	PR	T798I^b
	N + F	L755S, L755P	SD	T862A, S310F
	N + F	G776V	SD	I767M
	N + F	L755S	PD*	D769H, D962H^a, K1171N^a, D1016Y^a, D1089Y^a

All data are from circulating tumor DNA sequencing performed by Guardant360 for both MutHER and SUMMIT trials unless noted otherwise. All patients except those marked with an asterisk (*) achieved clinical benefit. ^aVariant of unknown significance. ^bGatekeeper mutation. ^cSynonymous mutation. ^dTissue samples, sequenced by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). CR: Complete response; F: fulvestrant; MBC: metastatic breast cancer; N: neratinib; PD: progressive disease; PR: partial response; SD: stable disease.