Table 3 Safety and tolerability of cabozantinib (safety population)
Child–Pugh B subgroup | Overall populationa | |||||||
|---|---|---|---|---|---|---|---|---|
Cabozantinib (N = 51) | Placebo (N = 22) | Cabozantinib (N = 467) | Placebo (N = 237) | |||||
Median duration of exposure (range), months | 3.7 (1.4–12.9) | 2.0 (0.9–5.5) | 3.8 (0.1–37.3) | 2.0 (0.0–27.2) | ||||
Median average daily dose (range), mg | 36.9 (12.5–60.0) | 56.8 (17.9–60.0) | 35.8 (1.1–60.0) | 58.9 (12.0–60.0) | ||||
Dose reduction, n (%) | 31 (61) | 3 (14) | 291 (62) | 30 (13) | ||||
Discontinuation due to treatment-related AE, n (%) | 9 (18) | 1 (5) | 74 (16) | 6 (2.5) | ||||
All-causality AE, n (%)b | Any grade | Grade 3/4 | Any grade | Grade 3/4 | Any grade | Grade 3/4 | Any grade | Grade 3/4 |
Any event | 51 (100) | 36 (71) | 22 (100) | 13 (59) | 460 (99) | 316 (68) | 219 (92) | 86 (36) |
Fatigue | 29 (57) | 10 (20) | 9 (41) | 4 (18) | 212 (45) | 49 (10) | 70 (30) | 10 (4.2) |
Ascites | 17 (33) | 7 (14) | 12 (55) | 5 (23) | 57 (12) | 18 (3.9) | 30 (13) | 11 (4.6) |
AST increased | 11 (22) | 7 (14) | 2 (9.1) | 1 (4.5) | 105 (22) | 55 (12) | 27 (11) | 16 (6.8) |
Thrombocytopenia | 11 (22) | 6 (12) | 0 | 0 | 52 (11) | 16 (3.4) | 1 (0.4) | 0 |
Anaemia | 6 (12) | 5 (9.8) | 5 (23) | 4 (18) | 46 (9.9) | 19 (4.1) | 19 (8.0) | 12 (5.1) |
Blood bilirubin increased | 11 (22) | 5 (9.8) | 3 (14) | 0 | 45 (9.6) | 14 (3.0) | 17 (7.2) | 4 (1.7) |
Dyspnoea | 10 (20) | 5 (9.8) | 7 (32) | 0 | 58 (12) | 15 (3.2) | 24 (10) | 1 (0.4) |
Blood ALP increased | 4 (7.8) | 4 (7.8) | 0 | 0 | 34 (7.3) | 16 (3.4) | 14 (5.9) | 1 (0.4) |
Hypertension | 9 (18) | 4 (7.8) | 0 | 0 | 137 (29) | 74 (16) | 14 (5.9) | 4 (1.7) |
PPE | 15 (29) | 4 (7.8) | 1 (4.5) | 0 | 217 (46) | 79 (17) | 12 (5.1) | 0 |
Platelet count decreased | 6 (12) | 4 (7.8) | 0 | 0 | 45 (9.6) | 17 (3.6) | 7 (3.0) | 2 (0.8) |
Portal vein thrombosis | 4 (7.8) | 4 (7.8) | 0 | 0 | 6 (1.3) | 5 (1.1) | 0 | 0 |
Pulmonary embolism | 4 (7.8) | 4 (7.8) | 0 | 0 | 7 (1.5) | 6 (1.3) | 5 (2.1) | 4 (1.7) |
Asthenia | 12 (24) | 3 (5.9) | 3 (14) | 0 | 102 (22) | 32 (6.9) | 18 (7.6) | 4 (1.7) |
Decreased appetite | 30 (59) | 3 (5.9) | 5 (23) | 0 | 225 (48) | 27 (5.8) | 43 (18) | 1 (0.4) |
Diarrhoea | 24 (47) | 3 (5.9) | 6 (27) | 1 (4.5) | 251 (54) | 46 (9.9) | 44 (19) | 4 (1.7) |
General physical health deterioration | 5 (9.8) | 3 (5.9) | 2 (9.1) | 2 (9.1) | 33 (7.1) | 21 (4.5) | 11 (4.6) | 6 (2.5) |
Hepatic encephalopathy | 4 (7.8) | 3 (5.9) | 0 | 0 | 19 (4.1) | 13 (2.8) | 3 (1.3) | 2 (0.8) |
Hyperbilirubinemia | 4 (7.8) | 3 (5.9) | 1 (4.5) | 0 | 11 (2.4) | 6 (1.3) | 8 (3.4) | 5 (2.1) |
Nausea | 23 (45) | 3 (5.9) | 6 (27) | 0 | 147 (31) | 10 (2.1) | 42 (18) | 4 (1.7) |
Pain | 3 (5.9) | 3 (5.9) | 0 | 0 | 19 (4.1) | 4 (0.9) | 5 (2.1) | 0 |
Pneumonia | 4 (7.8) | 3 (5.9) | 1 (4.5) | 0 | 24 (5.1) | 14 (3.0) | 7 (3.0) | 3 (1.3) |
Abdominal pain | 11 (22) | 2 (3.9) | 10 (45) | 3 (14) | 83 (18) | 8 (1.7) | 60 (25) | 10 (4.2) |
Hepatic failure | 3 (5.9) | 1 (2.0) | 3 (14) | 3 (14) | 9 (1.9) | 2 (0.4) | 8 (3.4) | 6 (2.5) |
Sepsis | 1 (2.0) | 1 (2.0) | 2 (9.1) | 2 (9.1) | 3 (0.6) | 2 (0.4) | 3 (1.3) | 3 (1.3) |
Additional events of interest | ||||||||
ALT increased | 7 (14) | 2 (3.9) | 1 (4.5) | 0 | 80 (17) | 23 (4.9) | 13 (5.5) | 5 (2.1) |
Hyponatremia | 5 (9.8) | 2 (3.9) | 0 | 0 | 26 (5.6) | 18 (3.9) | 9 (3.8) | 5 (2.1) |
Neutrophil count decreased | 2 (3.9) | 1 (2.0) | 0 | 0 | 17 (3.6) | 6 (1.3) | 5 (2.1) | 1 (0.4) |
Hypoalbuminemia | 17 (33) | 1 (2.0) | 2 (9.1) | 0 | 55 (12) | 2 (0.4) | 12 (5.1) | 0 |
Chronic hepatic failure | 0 | 0 | 1 (4.5) | 0 | 0 | 0 | 1 (0.4) | 0 |