Table 1.
Selected phase III clinical trials for postmenopausal women with hormone receptor-positive locally advanced or metastatic breast cancer
| Study design | Treatment comparison | Patients, n | PFS, months: experimental vs. control arm | Hazard ratio (95% CI) | Median follow-up, months | OS, months: experimental vs. control arm | Hazard ratio (95% CI) | Most common adverse events, %: experimental vs. control arm | |
|---|---|---|---|---|---|---|---|---|---|
| First-line studiesa | |||||||||
| PALOMA-2 [35, 44] | R, DB, PC | Letrozole + palbociclib vs. letrozole + placebo | 666 | 27.6 vs. 14.5 | 0.56 (0.46–0.69) |
37.6 (letrozole + palbociclib) 37.3 (letrozole + placebo) |
NA | – |
Neutropenia, 79.5 vs. 6.3 Leukopenia, 39.0 vs. 2.3 Fatigue, 37.4 vs. 27.5 Nausea, 35.1 vs. 26.1 |
| MONALEESA-2 [36, 45] | R, DB, PC | Letrozole + ribociclib vs. letrozole + placebo | 668 | 25.3 vs. 16.0 | 0.57 (0.46–0.70) | 26.4 | NR vs. 33.0 months | 0.75 (0.52–1.08) |
Neutropenia, 74.3 vs. 5.2 Nausea, 51.5 vs. 28.5 Infections, 50.3 vs. 42.4 Fatigue, 36.5 vs. 30.0 |
| MONALEESA-3a [40, 52] | R, DB, PC | Fulvestrant + ribociclib vs. fulvestrant + placebo | 726 | 20.5 vs. 12.8 | 0.59 (0.48–0.73) | NA | NR vs. 40.0g | 0.72 (0.57–0.92) |
Neutropenia, 69.6 vs. 2.1 Nausea, 45.3 vs. 28.2 Fatigue, 31.5 vs. 33.2 Diarrhea, 29.0 vs. 20.3 |
| FALCON [15] | R, DB | Fulvestrant vs. anastrozole | 524 | 16.6 vs. 13.8 | 0.8 (0.64–1.00) | NA | NA | 0.88 (0.63–1.22) |
Arthralgia, 16.7 vs. 10.3 Hot flush, 11.4 vs. 10.3 Fatigue, 11.4 vs. 6.9 Nausea, 10.5 vs. 10.3 |
| MONARCH 3 [39] | R, DB, PC | AI + abemaciclib vs. AI + placebo | 493 | NR vs. 14.7 | 0.54 (0.41–0.72) | 17.8 | NA | – |
Diarrhea, 81.3 vs. 29.8 Neutropenia, 41.3 vs. 1.9 Fatigue, 40.1 vs. 31.7 Infections and infestations, 39.1 vs. 28.6 |
| Second-line studiesa | |||||||||
| PALOMA-3b [41, 50] | R, DB, PC | Fulvestrant + palbociclib vs. fulvestrant + placebo | 413 | 9.9 vs. 3.9 | 0.45 (0.34–0.59) | 8.9 | 34.9 vs. 28.0f,g | 0.81 (0.64–1.03)g |
Neutropenia, 79.6 vs. 2.9 Infections, 40.1 vs. 29.4 Fatigue, 40.1 vs. 27.9 Nausea, 30.3 vs. 25.0 |
| MONARCH 2c [37, 51] | R, DB, PC | Fulvestrant + abemaciclib vs. fulvestrant + placebo | 669 | 16.4 vs. 9.3 | 0.55 (0.45–0.68) | 19.5 | 46.7 vs. 37.3f | 0.76 (0.61–0.95)g |
Diarrhea, 86.4 vs. 24.7 Nausea, 45.1 vs. 22.9 Fatigue, 39.9 vs. 26.9 Neutropenia, 46.0 vs. 4.0 |
| BOLERO-2d [38, 57] | R, DB, PC | Exemestane + everolimus vs. exemestane + placebo | 724 | 7.8 vs. 3.2 | 0.45 (0.38–0.54) | 17.7 | 31.0 vs. 26.6g | 0.89 (0.73–1.10) |
Stomatitis, 59 vs. 12 Rash, 39 vs. 7 Fatigue, 37 vs. 27 Diarrhea, 34 vs. 19 |
| SOLAR-1 [18, 64, 65] | R, DB, PC | Fulvestrant + alpelisib vs. fulvestrant + placebo | 572e | 11.0 vs. 5.7 | 0.65 (0.50–0.85) | 20.0 | NR vs. 26.9 | 0.73 (0.48–1.10) |
Hyperglycemia, 63.7 vs. 9.8 Diarrhea, 57.7 vs. 15.7 Nausea, 44.7 vs. 22.3 Decreased appetite, 35.6 vs. 10.5 |
ABC advanced breast cancer, AI aromatase inhibitor, CI confidence interval, DB double-blind, ET endocrine therapy, MBC metastatic breast cancer, NA not available, NR not reached, OS overall survival, PC placebo-controlled, PFS progression-free survival, R randomized
aIn the MONALEESA-3 study, some patients received up to one previous line of ET; however, approximately 50% of patients had not received treatment for ABC
bDisease relapse or progression after previous ET for ABC during treatment or within 12 months of completion of adjuvant therapy
cPatients had progressed while receiving neo-adjuvant or adjuvant ET, ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for MBC. Results are presented for the overall intent-to-treat population, which included pre- and perimenopausal patients
dPatients had recurrence or progression while receiving previous therapy with a non-steroidal AI in the adjuvant setting or to treat ABC (or both)
eIn total, 572 patients were enrolled; however, 341 patients were included in the PFS analysis
fOS and hazard ratio data shown are for the whole study population and are not split by menopausal status
gOS data shown are mature