Table 1.
Clinical trials of CDK4/6 inhibitors in breast cancer
| CDK inhibitors | Study ID | Phase | Lines | Patients | Regimens | Efficacy |
|---|---|---|---|---|---|---|
| Palbociclib | PALOMA-1 [25] | II | First-line | HR+/HER2− ABC | Palbociclib + letrozole (n = 84)/letrozole (n = 81) | mPFS 20.2 m vs 10.2 m, HR 0.488, 95% CI 0.319–0.748, p = 0.0004 |
| PALOMA-2 [36] | III | First-line | HR+/HER2− ABC | Palbociclib + letrozole (n = 444)/letrozole (n = 222) | mPFS 24.8 m vs 14.5 m, HR 0.58, 95% CI 0.46–0.72, p < 0.001 | |
| PALOMA-3 [30] | III | First/second-line | HR+/HER2− ABC with previous ET | Palbociclib + fluvastatin (n = 347)/fluvastatin (n = 174) | mOS 34.9 m vs 28.0 m, HR 0.81, 95% CI 0.64–1.03, p = 0.09 | |
| NCT01684215 [37] | II | First-line | Postmenopausal Japanese patients with HR+/HER2− ABC | Palbociclib + letrozole (n = 42) | PFS at 1 year 75.0%, mPFS NR, ORR 40.5%, DCR 85.75% | |
| NCT02592746 (active, not recruiting) | II | First/second/third-line | Premenopausal Women With HR+ MBC | Palbociclib + exemestane + leuprolide acetate/capecitabine (N = 182) | mPFS 9.2 m vs 3.8 m, p < 0.001 | |
| Ribociclib | MONALEESA-2 [38] | III | First-line | Postmenopausal women with HR+/HER2− ABC | Ribociclib + letrozole (n = 334)/letrozole (n = 334) | mPFS NR vs 14.7 m, HR 0.56, 95% CI 0.43–0.72, p < 0.001 |
| MONALEESA-3 [39] | III | First/second-line | HR+/HER2− ABC | Ribociclib + fulvestrant (n = 484)/fulvestrant (n = 242) | mPFS 20.5 m vs 12.8 m, HR 0.59, 95% CI 0.48–0.73, p < 0.001 | |
| MONALEESA-7 [40] | III | First/second-line | Premenopausal women with HR+/HER2− ABC | Ribociclib + ET (n = 335)/ET (n = 337) | mPFS 23.8 m vs 13.0 m, HR 0.55, 95% CI 0.44–0.69, p < 0.001 | |
|
TRINITI-1 NCT02732119 (active, not recruiting) |
I/II | Non-first line | Patients with HR+/HER2− ABC | Ribociclib + everolimus + exemestane (n = 107) | mPFS 5.7 m, ORR 8.4% | |
| Abemaciclib | MONARCH-1 [35] | II | Non-first line | Refractory HR+/HER2− ABC | Abemaciclib (n = 132) | ORR 19.7%, clinical benefit rate (CR + PR + SD ≥ 6.0 m) 42.4%, mPFS 6.0 m, mOS 17.7 m |
| MONARCH-2 [31] | III | Non-first line | HR+/HER2− ABC | Abemaciclib + fulvestrant (n = 446)/fulvestrant (n = 223) | mPFS 16.4 m vs 9.3 m, HR 0.55, 95% CI 0.45–0.68, p < 0.001 | |
| MONARCH 3 [33] | III | First-line | Postmenopausal women with HR+/HER2− ABC | Abemaciclib + nonsteroidal AI (n = 223)/nonsteroidal AI (n = 223) | mPFS NR vs 14.7 m, HR 0.54, 95% CI 0.41–0.72, p < 0.001, ORR 59% vs 44%, p = 0.004 |
ABC advanced breast cancer, MBC metastatic breast cancer, ET endocrine therapy, AI aromatase inhibitor, NR not reached, PFS progression-free survival, OS overall survival, ORR objective response rate, DCR disease control rate, HR hazard ratio