TABLE 2.
Summary of Adverse Events in all Treated Patients
| Event | Lenvatinib + Pembrolizumab (n = 238) | Standard of Care (n = 235) | ||
|---|---|---|---|---|
| Any adverse event, No. (%) | 237 (100) | 230 (98) | ||
| Treatment-related events, No. (%) | 226 (95) | 201 (86) | ||
| Grade 3 to 4 | 138 (58) | 99 (42) | ||
| Led to discontinuation of any drug | 30 (13) | 5 (2) | ||
| Led to deatha | 2 (1) | 0 | ||
| Adverse events of interest, No. (%) | 115 (48) | 23 (10) | ||
| Treatment-related events ≥10% in any armb, No. (%) | Any | Grade ≥3 | Any | Grade ≥3 |
| Hypertension | 117 (49) | 58 (24) | 34 (14) | 14 (6) |
| Proteinuria | 101 (42) | 26 (11) | 19 (8) | 1 (<1) |
| Hypothyroidism | 85 (36) | 1 (<1) | 12 (5) | 0 |
| Diarrhea | 84 (35) | 16 (7) | 45 (19) | 8 (3) |
| Fatigue | 55 (23) | 5 (2) | 42 (18) | 4 (2) |
| Decreased appetite | 52 (22) | 1 (<1) | 43 (18) | 4 (2) |
| Palmar-plantar erythrodysesthesia syndrome | 45 (19) | 7 (3) | 45 (19) | 8 (3) |
| Dysphonia | 43 (18) | 0 | 19 (8) | 1 (<1) |
| Aspartate aminotransferase increased | 38 (16) | 5 (2) | 16 (7) | 1 (<1) |
| Asthenia | 36 (15) | 6 (3) | 27 (11) | 2 (1) |
| Nausea | 36 (15) | 1 (<1) | 52 (22) | 3 (1) |
| Platelet count decreased | 36 (15) | 5 (2) | 20 (9) | 2 (1) |
| Vomiting | 36 (15) | 2 (1) | 26 (11) | 2 (1) |
| Alanine aminotransferase increased | 32 (13) | 4 (2) | 12 (5) | 2 (1) |
| Rash | 26 (11) | 3 (1) | 10 (4) | 2 (1) |
| Arthralgia | 25 (11) | 3 (1) | 2 (1) | 0 |
| Stomatitis | 23 (10) | 2 (1) | 10 (4) | 1 (<1) |
| Anemia | 14 (6) | 3 (1) | 30 (13) | 7 (3) |
| Neutropeniac | 8 (3) | 4 (2) | 31 (13) | 23 (10) |
| Neutrophil count decreased | 6 (3) | 1 (<1) | 30 (13) | 23 (10) |
| Adverse events of interestd, No. (%) | ||||
| Hypothyroidism | 90 (38) | 1 (<1) | 16 (7) | 0 |
| Hyperthyroidism | 11 (5) | 0 | 2 (1) | 0 |
| Colitis | 5 (2) | 3 (1) | 0 | 0 |
| Adrenal insufficiency | 4 (2) | 0 | 1 (<1) | 0 |
| Hepatitis | 3 (1) | 1 (<1) | 0 | 0 |
| Infusion reactions | 3 (1) | 1 (<1) | 0 | 0 |
| Myositis | 2 (1) | 0 | 0 | 0 |
| Nephritis | 1 (<1) | 1 (<1) | 0 | 0 |
| Pancreatitis | 3 (1) | 3 (1) | 1 (<1) | 1 (<1) |
| Pneumonitis | 5 (2) | 4 (2) | 1 (<1) | 1 (<1) |
| Severe skin reactions | 7 (3) | 5 (2) | 3 (1) | 3 (1) |
| Thyroiditis | 5 (2) | 0 | 0 | 0 |
| Type 1 diabetes mellitus | 1 (<1) | 1 (<1) | 0 | 0 |
NOTE. The as-treated population included all patients who were randomly assigned and received at least one study treatment. Percentages may not total 100 because of rounding.
Grade 5 treatment-related events occurred in two patients in the lenvatinib plus pembrolizumab arm because of pneumonitis and cerebral hemorrhage in one patient each.
Reported are treatment-related adverse events that occurred in at least 10% of patients in any group. Grade 3 or greater events among these events are reported.
Neutropenia is the clinical diagnosis resulting from decreased neutrophil count. Both are reported here separately.
Adverse events of interest (immune-mediated adverse events and infusion reactions) were based on a list of terms specified by the sponsor, regardless of attribution to any study treatment by investigators. All adverse events of interest are reported.