Optimal Choice of Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer: Clinical Insights

Figures & data

Table 1 Improvements in pCR with the Addition of Platinum and Immunotherapeutic Agents

Study		Intervention Arm	Intervention Arm	Control Arm
Addition of a carboplatin to standard taxane-anthracycline backbone
BrighTNess^Citation17 (NCT02032277) N=634
		WP x 12 + Cb q3w x 4 + velip →AC q2-3w x 4 → Sx	WP x 12 + Cb q3w x 4 + velip pbo →AC q2-3 w x 4 →	WP + Cb pbo q3w x 4 + velip pbo →AC q2-3w x 4 → Sx
	pCR (%)	58	53	31
	4-year EFS %	78.2	79.3	68.5
Addition of an immune check point inhibitor to standard neoadjuvant taxane-anthracycline backbone
GeparNuevo^Citation27,Citation58 (NCT02685059) N=174
		Durva 2w pre chemo (window-phase) →durva q4w + nab-pac q1w x 12 →durva q4w + EC q2 w x 4 → Sx		Pbo durva 2w window phase →durva pbo q4w + nab-pac q1w x 12 →durva pbo q4 w + EC x 4 → Sx
	pCR (%)
	Overall	53.4		44.2
	PD-L1 negative	44.4		18.2
	PD-L1 positive	58.0		50.7
	3-year iDFS	84.9		76.9 79.5 83.1
	3-year DDFS	91.4
	3-year OS	95.1
I-SPY2^Citation9 (NCT01042379) N= 29 TNBC (pembro) N=180 control population		WP x 12 + pembro x 4 q3w →AC x 4 q2-3w		WP x 12→AC x 4 q2-3w
	Estimated pCR (%)
	Overall	60		22
Addition of immune check point inhibitor to platinum, taxane, anthracycline backbone followed by adjuvant ICI
KEYNOTE-522^Citation20,Citation30 (NCT03036488) N=1174
		Pembro q3w + WP and Cb for 12w → 4 x q3w pembro and 4 x AC or EC → Sx →q3w pembro x 9		Pembo Pbo q3w + WP and Cb for 12w →4 x q3w pembro pbo and 4 x AC or EC → Sx →q3w pembro pbo x 9
	pCR (%)
	Overall	64.8		51.2
	PD-L1 negative	45.3		30.3
	PD-L1 positive	68.9		54.9
3-year EFS		84.5		76.8
Addition of immune check point inhibitor to taxane, anthracycline backbone followed by adjuvant ICI
IMpassion031^Citation28 (NCT03197935) N=455
		Atezo q2w + nab-pac q1w x 12 → AC q2w x 4 + Atezo q2w → Sx → atezo q3 w x 11		Pbo q2w + nab-pac q1w x 12 → AC q2w x 4 + pbo q2w → Sx → monitored *
	pCR (%)
	Overall	58		41
	PD-L1 negative	48		34
	PD-L1 positive	69		49
Addition of immune check point inhibitor to neoadjuvant platinum-taxane-regimen followed by surgery then the anthracycline component
NeoTRIPaPDL1^Citation29 (NCT002620280) N=280
		Cb AUC 2 and nab-pac d1, 8 q3w x 8 + atezo q3w x 8→ surgery → anthra regimen x 4		Cb AUC 2 and nab-pac d1,8 q 3w x 8 → surgery → anthra regimen x 4
	pCR (%)
	Overall
	PD-L1 negative	33.9		35.4
	PD-L1 positive	59.5		51.9 69.2
	PD-L1 2+/3+	71.4

Notes: *Patients not achieving pCR in either arm could follow standard-of-care guidelines, including the use of adjuvant capecitabine. Patients randomly assigned to the atezolizumab plus chemotherapy group could continue to receive atezolizumab concomitantly with this adjuvant therapy. PD-L1 testing by Trial: GeparNUEVO: used VENTANA SP263 antibody and evaluated PD-L1 expression as percentage of tumour cells with membranous staining (PD-L1-TC) and percentage of TILs with membranous or cytoplasmic staining (PD-L1-IC; relative to total TILs). PD-L1 positivity was defined as ≥1% in one or both of these percentages. KEYNOTE-522: used IHC 22C3 pharmDx assay (Agilent Technologies). Expression was characterized according to the combined positive score (CPS), defined as the number of PD-L1–positive cells (tumor cells, lymphocytes, and macrophages) divided by the total number of tumor cells multiplied by 100; specimens with a combined positive score of 1 or greater were considered PD-L1–positive. IMpassion031: used VENTANA SP142 assay, with PD-L1 positive defined as PD-L1-expressing tumor infiltrating immune cells covering 1% or more of the tumour area. NeoTRIP: used the VENTANA SP142 assay with PD-L1 positive defined as PD-L1 expression in IC testing [yes (IC 1+, 2+, 3+) versus no (IC0)]. The PD-L1 scoring was defined as follows: IC 0 (IC <1%),C 1+ (IC ≥1% and <5%) and IC 2+/3+ (IC ≥5%).

Abbreviations: pCR, pathological complete response; WP, weekly paclitaxel; Cb, carboplatin; velip, veliparib; q3w, every three weeks; q2-3w, every two to three weeks; AC, doxorubicin and cyclophosphamide; pbo, placebo; Sx, surgery; Durva, durvalumab; nab-pac, nabpaclitaxel; EC, epirubicin and cyclophosphamide; Pembro, pembrolizumab; Atezo, atezolizumab; anthra, anthracycline; EFS, event free survival; DFS, disease free survival; iDFS, invasive DFS; DDFS, distant DFS; PD-L1, programmed death-ligand.

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