Table 1.
Selected randomized phase III trials of CDK4/6 inhibitors in the first line setting.
| PALOMA-2 [1,35] | MONALEESA-2 [2] | MONALEESA-7 [36] | MONARCH-3 [3,4] | |
|---|---|---|---|---|
| Regimen | Letrozole ± palbociclib (2:1) | Letrozole ± ribociclib (1:1) | Goserelin + AI or tamoxifen ± ribociclib (1:1) | AI ± abemaciclib (2:1) |
| Eligibility | Postmenopausal women with untreated advanced HR+/HER2- BC | Postmenopausal women with untreated advanced HR+/HER2- BC | Pre/perimenopausal women with untreated advanced HR+/HER2- BC | Postmenopausal women with untreated advanced HR+/HER2- BC |
| Sample size | 666 | 668 | 672 | 493 |
| De novo metastatic disease | 38% | 34% | 41% | 20% |
| Median PFS (CDK vs. placebo) | 27.6 vs. 14.5 months (HR = 0.56, 95%CI 0.46–0.69) | 25.3 vs. 16 months (HR = 0.57; 95%CI 0.45–0.60 | 23.8 vs. 13 months (HR = 0.55, 95%CI 0.44–069) | 28.2 vs. 14.8 (HR-0.53; 95%CI 0.42–0.66) |
| Median OS(CDK vs. placebo) | 53.9 vs. 51.2 months (HR = 0.96; 95%CI 0.77–1.17)a | 63.9 vs. 51.4 months (HR = 0.76 95%CI 0.63–0.93) | 58.7 vs. 48 months (HR 0.76; 95%CI 0.60–0.95) | 53.7 vs. 66.8 months (HR 0.84; 95%CI 0.637–1.01)b |
| Toxicities of interest | Neutropenia, leukopenia, fatigue, nausea, arthralgia, diarrhea | Neutropenia, leukopenia, fatigue, nausea, QTc prolongation, transaminitis | Neutropenia, leukopenia, fatigue, nausea, QTc prolongation, transaminitis | Diarrhea, neutropenia, fatigue, nausea, anemia, abdominal pain |
Abbreviations: AI: aromatase inhibitor; BC: breast cancer; HER2: human epidermal growth factor receptor 2; HR: hazard ratio; HR+: hormone receptor positive; OS: overall survival; PFS: progression free survival.
a
22% of patients had a disease-free interval off less than 12 months, in the other trials, it ranged from 0 to 7%.
b
Not statistically significant, p = 0.0664, it was a secondary endpoint.