Background
Methods
Study design and patients
Treatment procedure
Efficacy and safety assessments
Endpoints
Statistical analyses
Results
Patients and treatment
Abemaciclib + fulvestrant N = 72 | Placebo + fulvestrant N = 42 | |
---|---|---|
Median age (range) | 46 (32–57) | 47 (32–66) |
Race, n (%) | ||
Asian | 51 (70.8) | 24 (57.1) |
Caucasian | 14 (19.4) | 16 (38.1) |
Other | 7 (9.7) | 2 (4.8) |
Most recent ET, n (%)a | ||
Neoadjuvant or adjuvant | 44 (61.1) | 21 (50.0) |
Metastatic | 26 (36.1) | 20 (47.6) |
Number of lines of ET, n (%) | ||
1 | 60 (83.3) | 30 (71.4) |
2 | 10 (13.9) | 11 (26.2) |
Prior AI, n (%) | ||
Yes | 10 (13.9) | 12 (28.6) |
No | 62 (86.1) | 30 (71.4) |
Sensitivity to ET, n (%)a | ||
Primary resistanceb | 28 (38.9) | 15 (35.7) |
Secondary resistancec | 42 (58.3) | 26 (61.9) |
Progesterone-receptor status, n (%) | ||
Positive | 54 (75.0) | 38 (90.5) |
Negative | 18 (25.0) | 4 (9.5) |
Metastatic site, n (%) | ||
Visceral | 43 (59.7) | 17 (40.5) |
Bone only | 19 (26.4) | 15 (35.7) |
Other | 10 (13.9) | 10 (23.8) |
Measurable disease, n (%) | ||
Yes | 51 (70.8) | 28 (66.7) |
No | 21 (29.2) | 14 (33.3) |
ECOG performance status | ||
0 | 54 (75.0) | 36 (85.7) |
1 | 18 (25.0) | 6 (14.3) |
Progression-free survival
Objective response rate and tumor shrinkage
Overall population | Abemaciclib + fulvestrant N = 72 | Placebo + fulvestrant N = 42 | P value | ||
---|---|---|---|---|---|
n (%) | 95% CI | n (%) | 95% CI | ||
CR | 2 (2.8) | − 1.0, 6.6 | 0 (0) | – | |
PR | 29 (40.3) | 28.9, 51.6 | 8 (19.0) | 7.2, 30.9 | |
SD | 30 (41.7) | 30.3, 53.1 | 27 (64.3) | 49.8, 78.8 | |
≥ 6 months | 25 (34.7) | 23.7, 45.7 | 21 (50.0) | 34.9, 65.1 | |
Progressive disease | 8 (11.1) | 3.9, 18.4 | 6 (14.3) | 3.7, 24.9 | |
Not evaluable | 3 (4.2) | − 0.4, 8.8 | 1 (2.4) | − 2.2, 7.0 | |
Overall response rate (CR + PR) | 31 (43.1) | 31.6, 54.5 | 8 (19.0) | 7.2, 30.9 | .009 |
Disease control rate (CR + PR + SD) | 61 (84.7) | 76.4, 93.0 | 35 (83.3) | 72.1, 94.6 | .845 |
Clinical benefit rate (CR + PR + SD ≥ 6 months) | 56 (77.8) | 68.2, 87.4 | 29 (69.0) | 55.1, 83.0 | .304 |
Measurable disease population | Abemaciclib + fulvestrant N = 51 | Placebo + fulvestrant N = 28 | P value | ||
---|---|---|---|---|---|
n (%) | 95% CI | n (%) | 95% CI | ||
CR | 2 (3.9) | − 1.4, 9.2 | 0 (0.0) | – | |
PR | 29 (56.9) | 43.3, 70.5 | 8 (28.6) | 11.8, 45.3 | |
SD | 11 (21.6) | 10.3, 32.9 | 16 (57.1) | 38.8, 75.5 | |
≥ 6 months | 7 (13.7) | 4.3, 23.2 | 12 (42.9) | 24.5, 61.2 | |
Progressive disease | 7(13.7) | 4.3, 23.2 | 4 (14.3) | 1.3, 27.2 | |
Not evaluable | 2 (3.9) | − 1.4, 9.2 | 0 (0.0) | – | |
Overall response rate (CR + PR) | 31 (60.8) | 47.4, 74.2 | 8 (28.6) | 11.8, 45.3 | .006 |
Disease control rate (CR + PR + SD) | 42 (82.4) | 71.9, 92.8 | 24 (85.7) | 72.8, 98.7 | .702 |
Clinical benefit rate (CR + PR + SD ≥ 6 months) | 38 (74.5) | 62.5, 86.5 | 20 (71.4) | 54.7, 88.2 | .768 |
Overall survival
Post-discontinuation therapy
Other exploratory endpoints
Safety
Adverse events (≥ 10% patients in either arm) | Abemaciclib + fulvestrant N = 71 | Placebo + fulvestrant N = 42 | ||||||
---|---|---|---|---|---|---|---|---|
All | G2 | G3 | G4 | All | G2 | G3 | G4 | |
Any, n (%) | 70 (98.6) | 20 (28.2) | 40 (56.3) | 4 (5.6) | 40 (95.2) | 17 (40.5) | 7 (16.7) | 0 |
Diarrhea | 62 (87.3) | 22 (31.0) | 8 (11.3) | 0 | 10 (23.8) | 1 (2.4) | 0 | 0 |
Neutropeniaa | 42 (59.2) | 9 (12.7) | 28 (39.4) | 2 (2.8) | 3 (7.1) | 1 (2.4) | 1 (2.4) | 0 |
Leukopenia | 31 (43.7) | 15 (21.1) | 12 (16.9) | 0 | 2 (4.8) | 1 (2.4) | 0 | 0 |
Infections and infestations | 31 (43.7) | 26 (36.6) | 1 (1.4) | 0 | 11 (26.2) | 7 (16.7) | 2 (4.8) | 0 |
Abdominal pain | 25 (35.2) | 2 (2.8) | 0 | 0 | 5 (11.9) | 2 (4.8) | 0 | 0 |
Anemia | 24 (33.8) | 15 (21.1) | 7 (9.9) | 0 | 1 (2.4) | 0 | 0 | 0 |
Headache | 24 (33.8) | 7 (9.9) | – | 0 | 13 (31.0) | 2 (4.8) | 0 | 0 |
Vomiting | 23 (32.4) | 5 (7.0) | 1 (1.4) | 0 | 3 (7.1) | 0 | 1 (2.4) | 0 |
Nausea | 20 (28.2) | 6 (8.5) | 1 (1.4) | 0 | 10 (23.8) | 3 (7.1) | 1 (2.4) | 0 |
Respiratory disorders | 16 (22.5) | 4 (5.6) | 1 (1.4) | 0 | 9 (21.4) | 1 (2.4) | 0 | 0 |
Pyrexia | 13 (18.3) | 0 | 0 | 0 | 6 (14.3) | 1 (2.4) | 0 | 0 |
Stomatitis | 13 (18.3) | 3 (4.2) | 0 | 0 | 9 (21.4) | 2 (4.8) | 0 | 0 |
Pruritus | 13 (18.3) | 1 (1.4) | 0 | 0 | 2 (4.8) | 0 | 0 | 0 |
Thrombocytopenia | 12 (16.9) | 4 (5.6) | 0 | 2 (2.8) | – | – | – | – |
Alanine aminotransferase increased | 11 (15.5) | 4 (5.6) | 3 (4.2) | 0 | 2 (4.8) | 0 | 0 | 0 |
Rash | 11 (15.5) | 2 (2.8) | 1 (1.4) | 0 | – | – | – | – |
Constipation | 10 (14.1) | 1 (1.4) | 1 (1.4) | 0 | 7 (16.7) | 0 | 0 | 0 |
Arthralgia | 10 (14.1) | 2 (2.8) | 1 (1.4) | 0 | 7 (16.7) | 2 (4.8) | 0 | 0 |
Injection site reaction | 10 (14.1) | 1 (1.4) | 0 | 0 | 5 (11.9) | 0 | 0 | 0 |
Dry skin | 10 (14.1) | 1 (1.4) | 0 | 0 | – | – | – | – |
Fatigue | 9 (12.7) | 3 (4.2) | 0 | 0 | 10 (23.8) | 4 (9.5) | 0 | 0 |
Edema peripheral | 9 (12.7) | 1 (1.4) | 0 | 0 | 2 (4.8) | 0 | 0 | 0 |
Hot flush | 8 (11.3) | 2 (2.8) | 0 | 0 | 3 (7.1) | 2 (4.8) | 0 | 0 |
Alopecia | 8 (11.3) | 1 (1.4) | 0 | 0 | – | – | – | – |
Aspartate aminotransferase increased | 8 (11.3) | 4 (5.6) | 1 (1.4) | 0 | 4 (9.5) | 1 (2.4) | 0 | 0 |