Table 3.
Adverse Events (Safety Population).*
| Event | Experimental (N = 426) | Control (N = 424) | ||
|---|---|---|---|---|
| Any Grade | Grade 3 or 4 | Any Grade | Grade 3 or 4 | |
| number of patients (percent) | ||||
| Any event | 425 (100) | 337 (79) | 424 (100) | 236 (56) |
| Diarrhea | 212 (50) | 24 (6) | 98 (23) | 15 (4) |
| Alanine aminotransferase increased | 208 (49) | 113 (27) | 82 (19) | 26 (6) |
| Aspartate aminotransferase increased | 195 (46) | 87 (20) | 73 (17) | 21 (5) |
| Fatigue | 123 (29) | 12 (3) | 120 (28) | 10 (2) |
| Palmar-plantar erythrodysesthesia | 119 (28) | 14 (3) | 21 (5) | 0 |
| Hypertension | 116 (27) | 43 (10) | 35 (8) | 13 (3) |
| Hypothyroidism | 113 (27) | 1 (<1) | 70 (17) | 0 |
| Decreased appetite | 109 (26) | 2 (<1) | 74 (17) | 2 (<1) |
| Nausea | 108 (25) | 5 (1) | 103 (24) | 8 (2) |
| Rash | 102 (24) | 10 (2) | 95 (22) | 3 (1) |
| Lipase increased | 100 (23) | 41 (10) | 64 (15) | 27 (6) |
| Asthenia | 99 (23) | 10 (2) | 65 (15) | 8 (2) |
| Pruritus | 99 (23) | 0 | 128 (30) | 1 (<1) |
| Amylase increased | 95 (22) | 23 (5) | 59 (14) | 12 (3) |
| Arthralgia | 76 (18) | 5 (1) | 70 (17) | 7 (2) |
| Pyrexia | 75 (18) | 2 (<1) | 56 (13) | 0 |
| Anemia | 70 (16) | 15 (4) | 84 (20) | 26 (6) |
| Vomiting | 69 (16) | 3 (1) | 67 (16) | 4 (1) |
| Blood creatinine increased | 68 (16) | 4 (1) | 57 (13) | 3 (1) |
| Stomatitis | 68 (16) | 6 (1) | 11 (3) | 0 |
| Abdominal pain | 66 (15) | 8 (2) | 38 (9) | 3 (1) |
| Headache | 64 (15) | 4 (1) | 55 (13) | 3 (1) |
| Constipation | 63 (15) | 0 | 61 (14) | 0 |
| Back pain | 59 (14) | 5 (1) | 59 (14) | 3 (1) |
| Dysphonia | 57 (13) | 0 | 13 (3) | 0 |
| Hyperthyroidism | 54 (13) | 2 (<1) | 50 (12) | 1 (<1) |
| Cough | 52 (12) | 1 (<1) | 50 (12) | 0 |
| Mucosal inflammation | 50 (12) | 2 (<1) | 15 (4) | 1 (<1) |
| Hyponatremia | 49 (12) | 13 (3) | 38 (9) | 12 (3) |
| γ-Glutamyltransferase increased | 45 (11) | 18 (4) | 26 (6) | 11 (3) |
| Blood bilirubin increased | 44 (10) | 7 (2) | 15 (4) | 3 (1) |
| Dyspnea | 44 (10) | 2 (<1) | 45 (11) | 10 (2) |
| Blood alkaline phosphatase increased | 43 (10) | 6 (1) | 15 (4) | 2 (<1) |
| Dysgeusia | 43 (10) | 0 | 16 (4) | 0 |
Patients were assigned to receive cabozantinib in addition to nivolumab and ipilimumab (experimental group) or placebo in addition to nivolumab and ipilimumab (control group). Shown are adverse events of any cause that occurred in at least 10% of the patients in either trial group from the first dose of any trial agent through 30 days after the last dose. The safety population included all the patients who received any amount of any trial agent. Events are listed in descending order of frequency in the experimental group. A grade 5 event of any cause occurred in 27 patients (6%) in the experimental group and in 34 (8%) in the control group. Adverse events were classified according to the Medical Dictionary for Regulatory Activities, version 23.0. The data-cutoff date was January 31, 2022.