Table 1.
Available data on phase III trials assessing the efficacy of CDK 4/6 inhibitors in combination with endocrine treatments in metastatic breast cancer
| Study design | PALOMA-2 |
MONALEESA-2 |
MONARCH-3 |
MONALEESA-7 |
PALOMA-3 |
MONARCH-2 |
Monaleesa-3 |
|---|---|---|---|---|---|---|---|
| Phase III Placebo-controlled First-line (n = 666) Postmenopausal |
Phase III Placebo-controlled First-line (n = 668) Postmenopausal |
Phase III Placebo-controlled First-line (n = 493) Postmenopausal |
Phase III Placebo-controlled First-line (n = 672) Premenopausal |
Phase III Placebo-controlled ≥Second-line (n = 521) Pre- and postmenopausal |
Phase III Placebo-controlled Second-line (n = 672) Pre- and postmenopausal |
Phase III Placebo-controlled First and second-line (n = 726) Postmenopausal |
|
| Endocrine therapy | Letrozole | Letrozole | NSAI | Tamoxifen NSAI/LHRHa |
Fulvestrant | Fulvestrant | Fulvestrant |
| CDK 4/6 inhibitor | Palbociclib | Ribociclib | Abemaciclib | Ribociclib | Palbociclib | Abemaciclib | Ribociclib |
| Prior therapy |
No prior systemic therapy for ABC Prior (neo)adjuvant ET: 56% Tam: 47% AI: 27.5% DFI since adjuvant ET: ≤12 months: 22% >12 months: 40% Prior (neo) adjuvant chemo: 48% |
No prior systemic therapy for ABC Prior (neo)adjuvant ET: 52.4% Tam: 42% AI: 30% DFI since adjuvant ET: ≤12 months: 1.2% >12 months: 64.7% Prior (neo) adjuvant chemo: 43.7% |
No prior systemic therapy for ABC Prior (neo)adjuvant ET: 45.7% AI: 26% Other: 19.8% DFI since adjuvant ET: ≤36 months: 28% >36 months: 62.7% Prior (neo) adjuvant chemo: 38% |
No prior ET Up to 1 CT for ABC Prior (neo)adjuvant ET: 38% DFI since adjuvant ET: ≤12 months: 30% >12 months: 7% Prior (neo) adjuvant chemo: 41% Prior chemo for ABC: 14% |
Prior ET: -(neo)adjuvant: 77% -ABC: 22% Prior AI: 85.3% Prior chemo for ABC: 30.8% Prior lines oftt for ABC: 0: 24.2% 1: 38% 2: 26% ≥3: 11.8% |
Prior ET: -(neo)adjuvant: 59% -ABC: 38.3% Prior AI: 71% Prior chemo for ABC: none. Prior lines of tt for ABC (only one line of ET permitted): 38.3% |
Prior ET: -(neo)adjuvant: 59.7% -ABC: 22.7% Prior AI: NA Prior chemo for ABC: none. Prior lines of tt for ABC (only one line of ET permitted): 48.8% |
| Patient population |
De novo: 37% Bone only: 23% Visceral: 48% |
De novo: 34% Bone only: 20.7% Visceral: 59% |
De novo: 41.2% Bone only: 21.3% Visceral: 52.4% |
De novo: 41% Bone only: 24% Visceral: 58% Premenopausal: 100% |
Prior sensitivity to ET: -yes: 79% -no: 21% Bone only: 24% Visceral: 59.4% Premenopausal: 20.7% |
Prior sensitivity to ET: -yes: 73% -no: 25% Bone only: 27.6% Visceral: 55% Premenopausal: 16% |
Prior sensitivity to ET: NA De novo: 20% Bone only: 21.3% Visceral: 60.5% Premenopausal: none |
| HR PFS | 0.58 | 0.56 | 0.54 | 0.55 | 0.46 | 0.55 | 0.59 |
| Median PFS (months) | 24.8 versus 14.5 | 25.3 versus 16.0 | 28 versus 14.7 | 23.8 versus 13.0 | 11.2 versus 4.6 | 16.4 versus 9.3 | 20.5 versus 12.8 |
| HR OS | 0.95 (NS) | 0.76 | NA | 0.71 | 0.81 (NS) | 0.75 | 0.73 |
| Median OS | 52.2 versus 53.9 | 63.9 versus 51.4 | NA | NR versus 40.9 | 34.8 versus 28 | 46.7 versus 37.3 | 53.7 versus 41.5 |
ABC, advanced breast cancer; AI, aromatase inhibitor; DFI, disease-free interval; CDK 4/6, cyclin-dependent kinase 4 and 6; chemo, chemotherapy; ET, endocrine therapy; HR, hazard ratio; LHRHa, luteinizing hormone-releasing hormon agonist; NA, not available; NSAI, non-steroidal aromatase inhibitor; NS, non significal; OS, overall survival; PFS, progression-free survival; Tam, tamoxifen.