Table 1. Clinical trials with CDK4/6 or biological agents in combination with endocrine treatment in neoadjuvant setting.

Trial	Phase	Experimental arm	Control arm	Duration of the treatments	N of patients	Primary endpoint	Results
NEOPAL (17)	II	L + P	FEC ×3 → D ×3	19 w	106	RCB0/I	7.7% vs. 15%
NeoPalAna (18)	II	ANA → ANA + P; ANA + P	–	5 mo.; 6 mo.	50	CCCA after 15 d	26% vs. 87% (P<0.001)
PALLET (19)	II	L → P; P → L; P + L	L alone	14 w	307	CRR; Ki-67 changes	54.3% vs. 49.5%; 4.1 vs. 2.2 (P<0.001)
MONALEESA-1 (20)	II	L + R (400 mg); L + R (600 mg)	L alone; L alone	N.A.	14	Ki-67 reduction rate	96% vs. 69%; 92% vs. 69%
NeoMONARCH (21)	II	ABE; ABE + ANA	ANA	14 w	223	Ki-67 reduction rate	92.6% vs. 63.2%
N007 (22)	II	L + P	–	16 w	20	CRR	CRR in 17/20 pts; CR in 8/20 pts
LORELEI (23)	II	L + taselisib	L + pl	16 w	334	CRR	Overall: 50% vs. 39%; PIK3CAm: 38% vs. 56%; overall: 2% vs. 1%; PIK3Cam: 1% vs. 0%
CORALLEEN (13)	II	R + L	AC → Pac	24 w	106	Low-ROR risk after surgery	46.9% vs. 46.1%
FELINE (24)	II	L + Ri; L + Rc	L	24 w	32; 28	PEPI score 0 at surgery	25.4% vs. 25.8%

L, letrozole; P, palbociclib; FEC, 5-fluoro-uracil, epirubicin and cyclophosphamide; D, docetaxel; Ri, ribociclib intermittent; Rc, ribociclib continuous; RCB, residual cancer burden; PEPI, Preoperative Endocrine Prognostic Index; ANA, anastrozole; CCCA, complete cell cycle arrest (Ki-67 <2.7%); CCR, clinical response rate (Ki-67 <2.7%); CR, complete response; pCR, pathological complete response; pl, placebo; Pac, paclitaxel; w, weeks; mo., months; N.A., not available.