Table 2.

Pivotal trials on the cyclin-dependent kinase (CDK)4/6 pathway.

Author, Year [Ref]	Trial	Study Design	N° Patients	Treatment Line	Drug	Primary Endpoints	Results
Finn, 2015 [62]	PALOMA-1/ TRIO-18	Phase II Open-label Randomized 1:1	165	1° line	LET plus PAL versus LET	PFS	20.2 versus 10.2 mo; p = 0.0004
Finn, 2016 [63]	PALOMA-2	Phase III Placebo-controlled Double-blind Randomized 2:1	666	1° line	LET plus PAL versus LET plus PBO	PFS	24.8 versus 14.5 mo; p < 0.001
Cristofanilli, 2016 [64]	PALOMA-3	Phase III Placebo-controlled Double-blind Randomized 2:1	521	Progressed on previous ET	F500 +/-LHRH analogue plus PAL versus F500 +/-LHRH analogue plus PBO	PFS	9.5 versus 4.6 mo; p < 0.0001
Hortobagyi, 2017 [67]	MONALEESA-2	Phase III Placebo-controlled Double-blind Randomized 1:1	668	1° line postmenopausal	LET plus RIB versus LET plus PBO	PFS	25.3 versus 16 mo; p < 0.001
Slamon, 2018 [68]	MONALEESA-3	Phase III Placebo-controlled Double-blind Randomized 2:1	726	Progressed on previous ET	F500 plus RIB versus F500 plus PBO	PFS	20.5 versus 12.8 mo; p < 0.001
Tripathy, 2018 [69]	MONALEESA-7	Phase III Placebo-controlled Double-blind Randomized 1:1	672	1° line premenopausal	TAM/LET/ANA plus LHRH analogue plus RIB versus TAM/LET/ANA plus LHRH analogue plus PBO	PFS	23.8 versus 13 mo; p < 0.0001
Dickler, 2017 [74]	MONARCH-1	Phase II Single agent Open-label	132	Progressed on previous ET	ABE	ORR	CR 0 PR 17.4 % SD 40.2 % PD 25.0%
Goetz, 2017 [76]	MONARCH-3	Phase III Placebo-controlled Double-blind Randomized 2:1	493	1° line	LET or ANA plus ABE versus LET or ANA plus PBO	PFS	28.18 versus 14.76 mo; p = 0.000002

Abbreviations: ABE: abemaciclib; ANA: anastrozole; CR: complete response; F500: fulvestrant; LET: letrozole; HR: hazard ratio; mo: months; N: number; NR: not reached; ORR: overall response rate, PAL: palbociclib, PD: progressive disease; PFS: progression- free survival; PR: partial response; PBO: placebo; RIB: ribociclib; SD: stable disease; TAM: tamoxifen.