Chemotherapy only (N=33) | Chemotherapy plus ipilimumab and Nivolumab (N=49) | Ipilimumab and nivolumab only cross-over (N=16) | ||||
All grades N (%) | Grade ≥3 N (%) | All grades N (%) | Grade ≥3 N (%) | All grades N (%) | Grade ≥3 N (%) | |
Any AE | 33 (100) | 16 (48) | 49 (100) | 41 (84) | 15 (94) | 4 (25) |
Any TRAE | 32 (97) | 13 (39) | 48 (98) | 36 (73) | 14 (88) | 3 (19) |
Any SAE | 13 (39) | 4 (12) | 31 (63) | 26 (53) | 5 (31) | 3 (19) |
Immune-related adverse events (irAE) | ||||||
Any irAE | 1 (3) | 0 | 32 (65) | 15 (31) | 8 (50) | 3 (19) |
Thyroid events | 1 (3) | 0 | 22 (45) | 1 (2) | 2 (13) | 0 |
Adrenocortical insufficiency/hypophysitis | 0 | 0 | 5 (10) | 5 (10) | 2 (13) | 0 |
Pneumonitis | 0 | 0 | 4 (8) | 1 (2) | 1 (6) | 0 |
Hepatitis | 0 | 0 | 3 (6) | 3 (6) | 2 (13) | 1 (6) |
Colitis/diarrhoea | 0 | 0 | 3 (6) | 2 (4) | 2 (13) | 1 (6) |
Type 1 diabetes mellitus | 0 | 0 | 2 (4) | 2 (4) | 0 | 0 |
Pancreatitis/lipase increased | 0 | 0 | 2 (4) | 2 (4) | 0 | 0 |
Rash | 0 | 0 | 1 (2) | 1 (2) | 1 (6) | 1 (6) |
Nephritis | 0 | 0 | 1 (2) | 0 | 0 | 0 |
Most common adverse events | ||||||
Fatigue | 16 (48) | 1 (3) | 27 (55) | 4 (8) | 6 (38) | 0 |
Lymphocyte count decreased | 15 (45) | 7 (21) | 32 (65) | 18 (37) | 0 | 0 |
Rash | 13 (39) | 3 (9) | 27 (55) | 8 (16) | 5 (31) | 1 (6) |
Nausea | 16 (48) | 0 | 26 (53) | 2 (4) | 2 (13) | 0 |
Constipation | 18 (55) | 1 (3) | 16 (33) | 0 | 0 | 0 |
Stomatitis | 12 (36) | 1 (3) | 20 (41) | 1 (2) | 2 (13) | 0 |
PPE | 10 (30) | 0 | 16 (33) | 2 (4) | 0 | 0 |
Neutrophil count decreased | 10 (30) | 5 (15) | 11 (22) | 3 (6) | 1 (6) | 0 |
Musculoskeletal pain | 2 (6) | 0 | 11 (22) | 0 | 5 (31) | 0 |
Fever | 2 (6) | 0 | 8 (16) | 2 (4) | 4 (25) | 0 |
Pruritus | 2 (6) | 0 | 3 (6) | 0 | 5 (31) | 0 |
Adverse events in the FAS population are graded according to NCI CTCAE V.4.0 and presented as N (%) by treatment arm. Individual adverse events are listed regardless of relation to study therapy. Repeated adverse events in the same subject are counted only once. The table includes all immune-related adverse events, defined as ‘adverse events of special interest’ according to the protocol, and all adverse events occurring in ≥25% of patients in any treatment group.
AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; FAS, full analysis set; NCI, National Cancer Institute; PPE, palmar-plantar erythrodysesthesia syndrome; SAE, serious AE; TRAE, treatment-related adverse event.