Pivotal trials in treatment of hormone receptor-positive, HER2-negative MBC with CDK4/6 inhibitors
| First-line treatment | Second-line treatment | First- and second-line treatments | ||||||
|---|---|---|---|---|---|---|---|---|
| PALOMA-2 | MONALEESA-2 | MONARCH-3 | MONALEESA-7 | PARSIFAL | PALOMA-3 | MONARCH-2 | MONALEESA-3 | |
| Design | Phase III, placebo controlled | Phase III, placebo controlled | Phase III, placebo controlled | Phase III, placebo controlled | Phase II, open label | Phase III, placebo controlled | Phase III, placebo controlled | Phase III, placebo controlled |
| Patients (n) | 666 post-menopausal | 668 post-menopausal | 493 post-menopausal | 672 pre-menopausal | 486 post-menopausal | 521 post-menopausal | 669 post-menopausal | 726 post-menopausal |
| CDK4/6 Inhibitor | Palbociclib | Ribociclib | Abemaciclib | Ribociclib | Palbociclib (control arm) | Palbociclib | Abemaciclib | Ribociclib |
| Endocrine partner | Letrozole | Letrozole | Anastrozole or letrozole | Letrozole, anastrozole or tamoxifen + goserelin | Letrozole or fulvestrant | Fulvestrant | Fulvestrant | Fulvestrant |
| Primary endpoint: PFS (CDK4/6 inhibitor + ET vs. ET) | ||||||||
| HR (95% CI; P value) | 0.58 (0.46–0.72; < 0.0001) | 0.56 (0.45–0.72; < 0.00000009) | 0.54 (0.41–0.70; 0.00002) | 0.55 (0.44–0.69; < 0.0001) | 1.13 (0.90–1.5; 0.321) | 0.46 (0.36–0.59; < 0.0001) | 0.55 (0.45–0.68; < 0.001) | 0.59 (0.48–0.73; < 0.001) |
| Median PFS (months) | 24.8 vs. 14.5 (Δ10.3) | 25.3 vs. 16 (Δ9.3) | 28 vs. 14.7 (Δ13.3) | 23.8 vs. 13 (Δ10.8) | 27.9 vs. 32.8 (Δ4.9) | 9.5 vs. 4.6 (Δ4.9) | 16.4 vs. 9.3 (Δ7.1) | 20.5 vs. 12.8 (Δ7.7) |
| Secondary endpoint: OS (CDK4/6 inhibitor + ET vs. ET) | ||||||||
| HR (95% CI; P value) | 0.71 (0.54–0.95; 0.00973) | 1 (0.7–1.5; 0.986) | 0.81 (0.64–1.03; 0.09) | 0.75 (0.61–0.95; 0.01) | 0.72 (0.57–0.92; 0.0045) | |||
| Median OS (months) | Not yet reported (August 2023) | Not yet reported (August 2021) | Not yet reported (July 2021) | NR vs. 40. 9 | 4-year OS 67.6% vs. 67.5% | 34.9 vs. 28 (Δ6.9) | 46.7 vs. 37.3 (Δ9.4) | NR vs. 40 |
HER2, human epidermal growth factor 2; MBC, metastatic breast cancer; CDK4/6, cyclin-dependent kinase 4/6; PFS, progression-free survival; ET, endocrine therapy; HR, hazards ratio; CI, confidence interval; OS, overall survival.