Table 4.
Hepatic events, venous thromboembolic events, interstitial lung disease, and change in creatinine in MONARCH 2 and MONARCH 3
| MONARCH 2 | MONARCH 3 | |||
|---|---|---|---|---|
| Characteristics | Abemaciclib + fulvestrant (n = 441) | Placebo + fulvestrant (n = 223) | Abemaciclib + NSAI (n = 327) | Placebo + NSAI (n = 161) |
| Hepatic events | ||||
| ALT increased, any grade | 59 (13.4) | 12 (5.4) | 57 (17.4) | 12 (7.5) |
| Grade ≥3 | 18 (4.1) | 4 (1.8) | 21 (6.4) | 3 (1.9) |
| ≥3×ULN and TBILI ≥2×ULN | 1 (0.2) | 1 (0.5) | 1 (0.3) | 0 (0) |
| Dose reduction | 7 (1.6) | 0 (0) | 8 (2.4) | 1 (0.6) |
| Discontinuation | 3 (0.7) | 1 (0.4) | 7 (2.1) | 0 (0) |
| AST increased, any grade | 54 (12.2) | 15 (6.7) | 55 (16.8) | 12 (7.5) |
| Grade ≥3 | 10 (2.3) | 6 (2.7) | 12 (3.7) | 2 (1.2) |
| ≥3×ULN and TBILI ≥2×ULN | 2 (0.5) | 2 (0.9) | 0 (0) | 0 (0) |
| Dose reduction | 2 (0.5) | 0 (0) | 0 (0) | 0 (0) |
| Discontinuation | 2 (0.5) | 1 (0.4) | 2 (0.6) | 0 (0) |
| Venous thromboembolic events | ||||
| Any grade | 21 (4.8) | 2 (0.9) | 20 (6.1) | 1 (0.6) |
| Grade ≥3 | 9 (2.0) | 1 (0.4) | 10 (3.1) | 1 (0.6) |
| Type of VTE | ||||
| PE | 11 (2.5) | 0 (0) | 11 (3.4) a | 1 (0.6) |
| DVT | 10 (2.3) | 2 (0.9) | 9 (2.8) | 0 (0) |
| Death | 0 (0) | 0 (0) | 3 (0.9) | 0 (0) |
| SAE | 8 (1.8) | 1 (0.4) | 9 (2.8) | 1 (0.6) |
| PE | 4 (0.9) | 0 (0) | 7 (2.1) b | 1 (0.6) |
| DVT | 4 (0.9) | 1 (0.4) | 4 (1.2) b | 0 (0) |
| Dose reduction | 2 (0.5) | 0 (0) | 0 (0) | 1 (0.6) |
| Discontinuation | 2 (0.5) | 0 (0) | 4 (1.2) c | 0 (0) |
| Anticoagulant treatment | 19 (4.3) | 0 (0) | 17 (5.3) | 0 (0) |
| VTE risk factors | ||||
| History of blood clots | 1 (0.2) | 0 (0) | 4 (1.2) | 0 (0) |
| Recent surgery | 3 (0.7) | 0 (0) | 2 (0.6) | 0 (0) |
| Lung metastases | 2 (0.5) | 1 (0.4) | 7 (2.1) | 0 (0) |
| Body mass index >30 | 3 (0.7) | 1 (0.4) | 3 (0.9) | 1 (0.6) |
| Age >65 | 10 (2.3) | 2 (0.9) | 12 (3.7) | 0 (0) |
| Interstitial lung disease/pneumonitis events | ||||
| Any grade | 9 (2.0) | 1 (0.4) | 17 (5.2) | 1 (0.6) |
| Grade ≥3 | 3 (0.7) | 0 (0) | 4 (1.2) | 0 (0) |
| Preferred term | ||||
| Pneumonitis | 8 (1.8) | 1 (0.4) | 9 (2.8) | 1 (0.6) |
| ILD | 0 (0) | 0 (0) | 4 (1.2) | 0 (0) |
| Pulmonary fibrosis | 0 (0) | 0 (0) | 4 (1.2) | 0 (0) |
| Organizing pneumonia | 1 (0.2) | 0 (0) | 0 (0) | 0 (0) |
| Death | 2 (0.5) | 0 (0) | 1 (0.3) | 0 (0) |
| SAE | 4 (0.9) | 0 (0) | 6 (1.8) | 0 (0) |
| Dose reduction | 0 (0) | 0 (0) | 2 (0.6) | 0 (0) |
| Discontinuation | 2 (0.4) | 0 (0) | 4 (1.2) | 0 (0) |
| Antibiotic treatment d | 6 (1.4) | 0 (0) | 4 (1.2) | 0 (0) |
| Corticosteroid treatment d | 2 (0.5) | 0 (0) | 7 (2.1) | 0 (0) |
| Creatinine increased, by laboratory assessment e | ||||
| Any grade | 427 (98.4) | 161 (73.5) | 308 (98.1) | 131 (84.0) |
| Grade 1 | 231 (53.2) | 154 (70.3) | 135 (43.0) | 124 (79.5) |
| Grade 2 | 191 (44.0) | 7 (3.2) | 166 (52.9) | 7 (4.5) |
| Grade 3 | 5 (1.2) | 0 (0) | 7 (2.2) | 0 (0) |
| Grade 4 | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Dose reduction | 2 (0.5) | 0 (0) | 8 (2.4) | 0 (0) |
| Dose omission | 6 (1.4) | 0 (0) | 6 (1.6) | 0 (0) |
| Discontinuation | 0 (0) | 0 (0) | 4 (1.2) | 0 (0) |
Data are presented as n (%).
Three patients experienced both PE and DVT.
Two patients with an SAE experienced both a PE and a DVT.
Includes three patients who died.
In MONARCH 2, two patients had both antibiotics and corticosteroids; in MONARCH 3, one patient had antibiotics and corticosteroids.
Percentages here are calculated based on denominator of number of patients who had creatinine laboratory assessments completed: 434 patients in the MONARCH 2 abemaciclib arm; 219 patients in the MONARCH 2 placebo arm; 314 patients in the MONARCH 3 abemaciclib arm; and 156 patients in the MONARCH 3 placebo arm.
Abbreviations: DVT, deep vein thrombosis; NSAI, nonsteroidal aromatase inhibitor; PE, pulmonary embolism; SAE, serious adverse event; TBILI, total bilirubin; ULN, upper limit of normal; VTE, venous thromboembolic event.