Predicting the Efficacy of HER2-Targeted Therapies: A Look at the Host

Table 1

Evaluation of HER2-addiction and immune biomarkers in randomized trials investigating anti-HER2 targeted therapies.

Drug	Setting	Trial	Treatment	pCR, % or DFS, HR (95% CI)	Addiction^†	Immune^Δ
Trastuzumab (H)	Neoadjuvant	Buzdar et al. [22]	FEC; FECH	26; 65	—	—
	Neoadjuvant	NOAH [60]	AP > P > CMF; APH > PH > CMFH	22; 43	Yes [94]	Yes [104]
	Neoadjuvant	GeparQuattro [61]	EC > D; EC > DH	16; 32	Yes [101]	Yes [107]
	Adjuvant	BCIRG 006 [69]	AC > D; AC > DH > H	1; 0.64 (0.53–0.78)	—	—
	Adjuvant	FinHER [66]	D(V) > FEC; D(V)H > FEC	1; 0.42 (0.21–0.83)	—	Yes [108]
	Adjuvant	HERA [65]	Ch; Ch > H	1; 0.76 (0.67–0.86)	—	—
	Adjuvant	NSABP B-31 [67]	AC > P; AC > PH	1; 0.52 (0.45–0.6)	No [97]; Yes [99]	No [110]
	Adjuvant	NCCTG N9831 [67]	AC > P; AC > PH	1; 0.52 (0.45–0.6)	—	Yes [103]; No [109]
Trastuzumab (H) and/or lapatinib (L)	Neoadjuvant	CHER-LOB [82]	PH > FECH; PL > FECL; PHL > FECHL	25; 26; 47	Yes [96]	Yes [96]
	Neoadjuvant	CALGB 40601 [84]	PH; PL; PHL	46; 32; 56	Yes [84]	—
	Neoadjuvant	GeparQuinto [106]	ECH > DH; ECL > DL	30; 23	—	Yes [107]
	Neoadjuvant	NeoALTTO [81]	PH; PL; PHL	29; 25; 51	Yes [95]	Yes [105]
	Neoadjuvant	NSABP B-41 [83]	AC > PH; AC > PL; AC > PHL	52; 53; 62	—	—
	Adjuvant	ALTTO [86]	PH; PHL	1; 0.84 (0.7–1.12)	—	—
Trastuzumab (H) and/or pertuzumab (Pz)	Neoadjuvant	NeoSphere [76]	DH; DPz; HPz; DHPz	29; 24; 17; 46	Yes [13]	Yes [104]
	Neoadjuvant	TRYPHAENA [77]	FEC > DHPz; FECHPz > DHPz; CDHPz	57; 62; 66	Yes [12]	—
	Adjuvant	APHINITY [78]	C(F)E > TH; C(F)E > THPz	1; 0.81 (0.66–1.00)	—	—

The comparison is statistically significant; ^†HER2-addiction as evaluated by PAM50 or ERBB2/ESR1 gene expression; ^Δimmune-related features as evaluated by TIL count or immune metagene. In these columns, it is indicated whether the biomarker is significantly associated (yes) or not (no) with outcome; A: adriamycin; C: cyclophosphamide; Ch: chemotherapy; D: docetaxel; DFS: disease-free survival; E: epirubicin; F: fluorouracil; H: trastuzumab; L: lapatinib; M: metotrexate; P: paclitaxel; pCR: pathological complete response; Pz: pertuzumab; T: taxanes; V: vinorelbine.