Table 3:
All-cause adverse events (≥10% cutoff) and immune-mediated adverse events in all treated patients in either treatment arm
| All-cause adverse events | ||||
|---|---|---|---|---|
| Nivolumab plus ipilimumab (N=404) |
Placebo (N=407) |
|||
| Event, n (%)* | Grade 1–2 | Grade 3–4† | Grade 1–2 | Grade 3–4 |
| Patients with any event | 237 (59) | 154 (38) | 319 (78) | 42 (10) |
| Pruritus | 126 (31) | 2 (<1) | 69 (17) | 0 |
| Fatigue | 120 (30) | 3 (<1) | 108 (27) | 1 (<1) |
| Diarrhoea | 95 (24) | 16 (4) | 83 (20) | 2 (<1) |
| Rash | 86 (21) | 5 (1) | 37 (9) | 1 (<1) |
| Headache | 69 (17) | 2 (<1) | 59 (14) | 0 |
| Nausea | 67 (17) | 2 (<1) | 50 (12) | 0 |
| Hyperthyroidism | 65 (16) | 1 (<1) | 5 (1) | 0 |
| Arthralgia | 64 (16) | 1 (<1) | 55 (14) | 0 |
| Hypothyroidism | 63 (16) | 2 (<1) | 20 (5) | 0 |
| Decreased appetite | 51 (13) | 1 (<1) | 8 (2) | 0 |
| Cough | 50 (12) | 0 | 52 (13) | 0 |
| Asthenia | 46 (11) | 2 (<1) | 31 (8) | 0 |
| Blood creatinine increased | 45 (11) | 1 (<1) | 37 (9) | 1 (<1) |
| Increased alanine aminotransferase | 35 (9) | 10 (2) | 12 (3) | 3 (<1) |
| Study treatment discontinuation due to an adverse event‡ | 47 (12) | 82 (20) | 1 (<1) | 8 (2) |
| Immune-mediated adverse events¶ | ||||
| Nivolumab plus ipilimumab (N=404) |
Placebo (N=407) |
|||
| Categories, n (%) | Grade 1–2 | Grade 3–4 | Grade 1–2 | Grade 3–4 |
| Hypothyroidism | 76 (19) | 2 (<1) | 13 (3) | 0 |
| Rash | 61 (15) | 10 (2) | 10 (2) | 2 (<1) |
| Hyperthyroidism | 62 (15) | 1 (<1) | 2 (<1) | 0 |
| Adrenal insufficiency | 24 (6) | 11 (3) | 2 (<1) | 0 |
| Hypophysitis | 18 (4) | 12 (3) | 0 | 0 |
| Diarrhoea/colitis | 15 (4) | 22 (5) | 3 (<1) | 0 |
| Hepatitis | 9 (2) | 14 (3) | 1 (<1) | 2 (<1) |
| Thyroiditis | 9 (2) | 2 (<1) | 0 | 0 |
| Pneumonitis | 7 (2) | 3 (<1) | 1 (<1) | 0 |
| Nephritis/renal dysfunction | 5 (1) | 5 (1) | 5 (1) | 1 (<1) |
| Diabetes mellitus | 1 (<1) | 8 (2) | 0 | 0 |
Shown are adverse events that occurred while patients were receiving the assigned treatment or within 30 days after the end of the trial treatment period of all treated patients. Events are listed in descending order of frequency in the nivolumab plus ipilimumab arm.
One grade 5 event occurred in the nivolumab plus ipilimumab treatment arm.
Includes events leading to discontinuation of either nivolumab or ipilimumab at any time; all discontinuation criteria apply to nivolumab, ipilimumab, and placebo.
Immune-mediated adverse events are defined as adverse events consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory aetiologies (eg, infection or tumour progression) have been ruled out. Includes all categories of immune-mediated adverse events reported in patients treated with nivolumab plus ipilimumab or placebo including diarrhoea/colitis, hepatitis, pneumonitis, nephritis/renal dysfunction, and rash, considered by investigators to be potentially immune-mediated, and met the following criteria: occurred within 100 days of the last dose, regardless of causality, treated with immune-modulating medication, had no clear alternate aetiology, or had an immune-mediated component. Adrenal insufficiency, hypophysitis, hypothyroidism/thyroiditis, hyperthyroidism, and diabetes mellitus were considered immune-mediated adverse events regardless of immune-modulating medication use, as these endocrine events were often managed without immune-modulating medication.