Table 1.
PFS and OS Results From First-Line Trials of CDK4/6i
| Trial | Patients, No. | CDK4/6i | ET | Design and study population | PFS | OS | Comments |
|---|---|---|---|---|---|---|---|
| PALOMA-1 (NCT00721409) | 165 | Palbociclib (P) | Letrozole (L) | Phase 2, postmenopausal women | 10.2 mo (L) vs 20.2 mo (L + P), HR, 0.488; 95% CI, 0.319–0.748; P < .001 | OS in the P + L vs L alone arm (37.5 mo vs 33.3 mo, respectively); HR, 0.813; 95% CI, 0.492–1. 345; P = .42 | No statistically significant OS advantage noted |
| PALOMA-2 (NCT01740427) | 666 | Palbociclib (P) | Letrozole (L) | Phase 3, postmenopausal women | 14.5 mo (L) vs 24.8 mo (L + P); HR, 0.58; 95% CI, 0.46–0.72; P < .001 | Median OS in the P + L vs L alone arm, 53.9 (95% CI, 49.8–60.8) mo vs 51.2 (95% CI, 43.7–58.9) mo; HR, 0.956; 95% CI, 0.777–1.177; stratified 1-sided P = .34 | No statistically significant OS advantage noted |
| MONARCH 3 (NCT02246621) | 493 | Abemaciclib (A) | NSAI | Phase 3, postmenopausal women | 14.76 mo (A) vs 28.18 mo (ET + A), HR, 0.54; 95% CI, 0.418–0.698; P < .001 | Mature OS data pending | NA |
| MONALEESA-2 (NCT01958021) | 668 | Ribociclib (R) | Letrozole (L) | Phase 3, postmenopausal women | 16.0 (95% CI, 13.4–18.2) mo (L) vs 25.3 (95% CI, 23.0–30.3) mo (L + R); HR, 0.568; 95% CI, 0.457–0.704; log-rank P = 9.63 × 10−8 | Median OS, 63.9 mo (R + L) vs 51.4 mo (L); HR, 0.76 | OS advantage seen |
| MONALEESA-7 (NCT02278120) | 672 | Ribociclib (R) | ET (Tam or AI) and OFS | Phase 3, pre- and perimenopausal women, previous ET permitted in (neo) adjuvant setting (chemotherapy also permitted in the [neo]adjuvant setting or for advanced BC) | Median PFS with R + ET was 23.8 mo vs 13.0 mo with ET + placebo (HR, 0.55; 95% CI, 0.44–0.69; P < .001) | OS at 42 mo: 70.2% (95% CI, 63.5%–76.0%) in R group and 46.0% (95% CI, 32.0%–58.9%) in placebo group (HR for death, 0.71; 95% CI, 0.54–0.95; P = .01 by log-rank test) | OS advantage seen |
| DAWNA-2 (NCT03966898) | 456 | Dalpiciclib | Letrozole, anastrozole | Phase 3, pre- and postmenopausal women, 2:1 randomization | Median PFS was significantly improved in the dalpiciclib arm (30.6 mo vs 18.2 mo; HR, 0.51; 1-sided P < .001) | OS data immature | NA |
Abbreviations: AI, aromatase inhibitor; BC, breast cancer; CDK4/6i, cyclin-dependent kinase 4/6 inhibitors; ET, endocrine therapy; HR, hazard ratio; NA, not applicable; NSAI, nonsteroidal aromatase inhibitor; OFS, ovarian function suppression; OS, overall survival; PFS, progression-free survival; Tam, tamoxifen.