Table 3

Efficacy of CDK4/6 inhibitors in the metastatic setting

Reference Therapy Phase Patient characteristics Number of patients Response rate Median PFS
months
Median OS
months
Palbociclib
Slamon et al 13 Letrozole + palbociclib vs letrozoleIHR+, HER2-postmenopausal MBC first line12PR 25%
SD 75%
Clark et al 14 Palbociclib + paclitaxelIRb-expression ABC (+men)
78% previous taxane
15+12 (dose expansion; new schedule)PR 41%
SD 30%
NR
DeMichele et al 49 PalbociclibPhase II84% HR+HER2- 5% OR+/HER2+11% HR-,HER2- MBC
65% ≥2 lines of hormonal therapy
76% ≥2 lines of chemotherapy
37PR 5%
CBR (SD≥6 months) 19%: HR+, HER2-: PR 6%
CBR (SD≥6 months) 29%
3.7 (1.9–5.1)
HR+/HER2-: 3.8 (1.9–5.8)
NR
Finn et al 16 36 Letrozole + palbociclib
Letrozole
Phase II
PALOMA-1
OR+, HER2-postmenopausal
ABC
First line
No adj therapy 52%/46%
Adj TAM 29%/30%
Adj AI 17%/17%
Adj chemotherapy 40%/46%
Part 2: + screened for CCND1 amplification and/or loss of p16
Part 1:66
Part 2: 99
(N=84):
RR 31%
CBR 68%
(N=81):
RR 26%
CBR 44%
Part 1: HR 0.299 (95% CI, 0.159 to 0.572; p=0.0001).
Part 2: PFS: 26.2 vs 7.5 HR 0.032 (95% CI, 0.19 to 0.56; p<0.001).
Part 2: PFS: 26.2 vs 7.5 HR 0.032 (95% CI, 0.19 to 0.56; p<0.001).
Part 1+2 (N=165): PFS: 20.2 vs 10.2 HR 0.488 (95% CI, 0.319 to 0.74; p=0.0004).
(N=61): 37.5 vs
33.3.
Finn et al 17 Palbociclib + letrozole
Letrozole
III, PALOMA-2
(2:1)
OR+, HER2−
Postmenopausal
ABC
first line
Prior ET 57%
666RR 42.1%
34.7% (p=0.031)
CBR (not defined) 84.9 vs 70.3; p <0.0001
24.8%
14.8%
HR 0.58 (95% CI 0.46 to 0.72; p<0.000001)
Data immature
Turner et al 59, Cristofanilli et al 18 Palbociclib + fulvestrant
Placebo + fulvestrant ± goselin
III, PALOMA-3 (2:1)HR+, HER2−
ABC
Relapse or PD on prior ET
Prior AI≈85%
Prior TAM≈60% ≤1 line of chemotherapy
347
174
19 (95% CI 15.0 to 23.6)
9 (4.9 13.8)(p=0.0019)
CBR (CR+PR+SD≥24 weeks)
67 (61.3–71.5)
40 (32.3–47.3) (p >0.0001)
9.5 (2.0–11.0)
4.6 (3.5–5.6)
(HR 0.46, 95% CI 0.36 to 0.59; p<0.0001)
NR
Abemaciclib
Tolaney et al 23 Abemaciclib +
(A) letrozole
(B) anastrozole (C) tamoxifen (D) exemestane
(E) exemestane + everolimus
(F) exemestane + trastuzumab
IHR+, HER2- (A–E) or HER2+ (F)
MBC
No prior chemotherapy (A–E) or ≥1 chemotherapy (F)
65AB (36 pts): DCR (duration NR): 67%
C (16 pts): 75%
Patnaik et al 22 Abemaciclib
Abemaciclib + fulvestrant
Phase I, 2 cohorts≥ first line
MBC
1 cohort unselected, median 7 prior therapies
2 cohort HR+ median 4 prior therapies
47
(36 HR+)
13
HR+:
PR 36% (25% confirmed)
PR 85% (62% confirmed)
Dickler et al 24 AbemaciclibPhase II (MONARCH 1)HR+, HER2-
MBC
Progressed on/after ET and chemotherapy (1–2 lines)
Median 3 lines
132RR (confirmed) 17.4%
CBR (CR+PR+SD≥6 months) 42.4%
5.7
Ribociclib
Juric et al 25 26 A1: Ribociclib + letrozole.
A2: alpelisib + letrozole
A3: Ribociclib + letrozole + alpelisib
Phase Ib/(II)OR+,HER2-postmenopausal
ABC
≥ first line in the dose expansion group
A1: 47 patients
A2: 7
A3: 36 (27 evaluable)
A1: RR 5%, CBR (SD≥24 weeks) 32% (previously treated) 39%, CBR 73% (treatment-naïve)
A2: Not relevant
A3: PR 22% (15% confirmed), SD 22% non-CR non-PD 22%
Bardia et al 27 Ribociclib + everolimus + exemestane
Ribociclib + exemestane
Ib/(II)OR+, HER2-
postmenopausal
ABC
70 (55 evaluable)
NR
CR 2%,
PR 9% (4%
confirmed)
Disease control 71%*
  • ABC, advanced breast cancer; Adj, adjuvant; CBR, clinical benefit rate; CR, complete response; ET, endocrine therapy;OR, oestrogen receptor; OS, overall survival; HR, hormone receptor; NR, not reported; NSAI, non-steroidal aromatase inhibitor, ORR, overall response rate; pts, patients; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD stable disease.