Neoadjuvant endocrine therapy: A potential strategy for ER-positive breast cancer

Table 3 The optimal targeted agents

Clinical trial	Treatment arms (n)	Duration	Primary endpoint	Response ( Primary endpoint)
Johnston et al[37], 2019 (PALLET)	(A) LET 14 w (103); (B) LET 2 w followed by LET + PAL 12 w (68); (C) PAL 2 w followed by LET + PAL (69); (D) LET + PAL 14 w (67); LET:2.5 mg/d PAL: 125 mg/d	14 wk	Clinical response by ultrasound and median log-fold change in Ki-67 expression	A vs B + C + D: 54.3% vs 49.5% (P = 0.2), -2.2 vs -4.1(P < 0.001)
Ma et al[38], 2017 (NeoPalAna)	ANA 1 mg/d (plus goserelin if premenopausal) followed by PAL 125 mg/d on C1D1 (50)	5 mo	CCCA (Ki67 < 2.7%) on palbociclib plus anastrozole	C1D1 vs C1D15: 26% vs 87% (P < 0.001)
Arnedos et al[40], 2018 (POP)	(A) PAL 125 mg/d (74); (B) placebo (26)	14 d	Antiproliferative response, defined as lnKi67 < 1 at day five	58% vs 12% (P < 0.001)
Curigliano et al[42], 2016 (MONALEESA-1)	(A) LET 2.5 mg/d (2); (B) LET 2.5 mg/d + RIB 400 mg/d (6); (C) LET 2.5 mg/d + RIB 600 mg/d (3)	14 d	mean decreases in the Ki67-positive cell fraction from baseline	(A) 69% (range 38%-100%); (B) 96% (range 78%-100%); (C) 92% (range 75%-100%)
Neo-MONARCH	(A) ANA 2 w; (B) abemaciclib 2 w; (C) ANA + abemaciclib 2 w followed by ANA+ abemaciclib 12 w	14 wk	Changes in Ki67 expression	Reduced Ki67 in patients 15% vs 59% vs 66%
Ma et al[46], 2017	ANA 1 mg/d (plus goserelin if premenopausal) followed by MK-2206 125 mg/w (16)	4 mo	pCR rate	0%
Baselga et al[48], 2009	(A) LET 2.5 mg/d+ placebo; (B) LET 2.5 mg/d+ everolimus 10 mg/d	4 mo	OR by clinical palpation	68.1% vs 59.1% (P = 0.062)

ER: Estrogen receptor; PR: Progesterone receptor; LET: Letrozole; ANA: Anastrozole; PAL: Palbociclib; RIB: Ribociclib; OR: Objective response; CCCA: Complete cell-cycle arrest; pCR: Pathological complete response; BCS: Breast-conserving surgery.