From: Recent advances of highly selective CDK4/6 inhibitors in breast cancer
Breast tumor type | Phase | Dosage | Response rate | NCT | Ref |
---|---|---|---|---|---|
Palbociclib | |||||
RB+ ABC N = 5 | I | Administrated in six dose escalation cohorts (standard 3 + 3 design) MTD and RP2D: 125 mg | SD: 20% (1/5) | NCT 00141297 | [84] |
ER+/HER2- ABC N = 9 | I | MTD: 125 mg; Palbociclib (125 mg QD, 3 weeks on/1 week off) plus letrozole (2.5 mg, continuous) | PR: 33% (2/6) SD: 33% (2/6) | NCT 01684215 | [83] |
ER+/HER2-ABC N = 165 | II | Palbociclib (125 mg QD, 3 weeks on/1 week off) plus letrozole (2.5 mg, continuous) | PFS: 20.2 months for the palbociclib plus letrozole group and 10.2 months for the letrozole group (HR 0.488, 95%CI 0.319-0.748; one-sided p = 0.0004) | NCT 00721409 | [88] |
RB+ MBC N = 37 | II | Palbociclib (125 mg QD, 3 weeks on/1 week off) | PR: 7% (2/28) SD: 50% (14/28) PFS: 3.8 months (1.9–5.8) for HR+/HER2- patients, 5.1 months (5.1–∞)for HR+/HER2+ patients, 1.5 months (0.62-∞) for HR-/HER2- patients, 4.5 months for HR+ patients, and 1.5 months for HR- patients | NCT 01037790 | [87] |
HR+/HER2-ABC N = 521 | III | Palbociclib (125 mg QD, 3 weeks on/1 week off) plus fulvestrant (500 mg IM every 2 weeks For the first three injections and then every 4 weeks), or matching placebo plus fulvestrant | PFS: 9.2 months (95%CI, 7.5 to ∞) for palbociclib plus fulvestrant group and 3.8 months (95%CI, 3.5 to 5.5) for placebo plus fulvestrant group (HR: 0.42; 95%CI,0.32 to 0.56; P < 0.001) | NCT 01942135 | [90] |
ER+/HER2-ABC N = 666 | III | Palbociclib (125 mg QD, 3 weeks on/1 week off) plus letrozole (2.5 mg, continuous) | PFS: 24.8 months for the palbociclib plus letrozole group and 14.5 months for the letrozole group (HR 0.488, 95%CI 0.319-0.748; one-sided p = 0.0004) | NCT 01740427 | [89] |
Ribociclib | |||||
RB+ ABC N = 20 | I | MTD: 900 mg QD for 3 weeks on/1 week off RDE: 600 mg QD For 3 weeks on/1 week off; Ribociclib: 600 mg QD 3 weeks on/1 week off or continuous | PR: 1 (1/20) (600 mg/day continuous) | NCT 01237236 | [85] |
HR+/HER2- RBC or MBC N = 668 | III | Ribociclib (600 mg QD 3 weeks on/1 week off) plus letrozole (2.5 mg QD) or matching placeboplus letrozole. | PFS: ribociclib group versus placebo group (0.56;95%CI, 0.43to 0.72, p < 0.001); ribociclib group versus placebo group (63.0% (95%CI, 54.6 to 70.3) and 42.2% (95%CI,34.8 to 49.5) after 18 months, OR: ribociclib Group versus placebo group (52.7% and 37.1%) | NCT 01958021 | [91] |
Abemaciclib | |||||
BC N = 66 | I | Abemaciclib (200 mg Q12H continuous for 4 weeks) | PR: 31% in HR+ patients and none in HR- patients SD: 50% in HR+ patients and 33% in HR- patients | NCT 01394016 | [75] |
ER-/PR-/HER2 + BC N = 1 | I | Abemaciclib (200 mg Q12H continuous for 4 weeks) | Tumor size decreases more than 30% from baseline | NCT 02014129 | [93] |