TABLE 3.
Treatment-Related Adverse Events Occurring in ≥5% of All the Treated Participants
| Adverse Event | Lenvatinib + Pembrolizumab + Chemotherapy (n = 441), No. (%) | Chemotherapy (n = 429), No. (%) | ||
|---|---|---|---|---|
| Any | Grade ≥3 | Any | Grade ≥3 | |
| Treatment-related eventsa | 430 (97) | 288 (65) | 394 (92) | 208 (48) |
| Neutrophil count decreased | 203 (46) | 105 (24) | 194 (45) | 97 (23) |
| Nausea | 171 (39) | 10 (2) | 173 (40) | 5 (1) |
| Diarrhea | 169 (38) | 20 (5) | 109 (25) | 9 (2) |
| Hypertension | 140 (32) | 49 (11) | 0 | 0 |
| Decreased appetite | 130 (29) | 11 (2) | 79 (18) | 4 (1) |
| Hypothyroidism | 121 (27) | 2 (<1) | 0 | 0 |
| Platelet count decreased | 117 (27) | 21 (5) | 172 (40) | 35 (8) |
| Fatigue | 103 (23) | 14 (3) | 61 (14) | 6 (1) |
| WBC count decreased | 102 (23) | 15 (3) | 89 (21) | 14 (3) |
| Anemia | 101 (23) | 17 (4) | 109 (25) | 25 (6) |
| PPES | 95 (22) | 14 (3) | 59 (14) | 7 (2) |
| Proteinuria | 92 (21) | 9 (2) | 1 (<1) | 0 |
| AST increased | 81 (18) | 11 (2) | 75 (17) | 5 (1) |
| Vomiting | 79 (18) | 10 (2) | 92 (21) | 8 (2) |
| ALT increased | 70 (16) | 16 (4) | 57 (13) | 5 (1) |
| Weight decreased | 70 (16) | 9 (2) | 43 (10) | 6 (1) |
| Peripheral neuropathy | 69 (16) | 1 (<1) | 100 (23) | 13 (3) |
| Stomatitis | 64 (15) | 7 (2) | 40 (9) | 2 (<1) |
| Peripheral sensory neuropathy | 54 (12) | 2 (<1) | 81 (19) | 6 (1) |
| Asthenia | 51 (12) | 6 (1) | 54 (13) | 1 (<1) |
| Mucosal inflammation | 51 (12) | 9 (2) | 26 (6) | 2 (<1) |
| Lipase increased | 46 (10) | 12 (3) | 27 (6) | 8 (2) |
| Rash | 44 (10) | 1 (<1) | 10 (2) | 0 |
| Pruritus | 42 (10) | 1 (<1) | 6 (1) | 0 |
| Constipation | 41 (9) | 0 | 40 (9) | 0 |
| Amylase increased | 40 (9) | 6 (1) | 19 (4) | 1 (<1) |
| Blood thyroid-stimulating hormone increased | 37 (8) | 0 | 2 (<1) | 0 |
| Blood bilirubin increased | 35 (8) | 6 (1) | 32 (7) | 6 (1) |
| Abdominal pain | 32 (7) | 3 (1) | 19 (4) | 3 (1) |
| Hyperthyroidism | 30 (7) | 1 (<1) | 4 (1) | 0 |
| Hypokalemia | 27 (6) | 6 (1) | 16 (4) | 3 (1) |
| Paraesthesia | 26 (6) | 1 (<1) | 36 (8) | 3 (1) |
| Dysgeusia | 25 (6) | 0 | 38 (9) | 0 |
| Blood alkaline phosphatase increased | 24 (5) | 4 (1) | 28 (7) | 3 (1) |
| Dry mouth | 24 (5) | 0 | 5 (1) | 0 |
| Arthralgia | 23 (5) | 3 (1) | 4 (1) | 0 |
| Dysphonia | 22 (5) | 0 | 3 (1) | 0 |
Abbreviation: PPES, palmar-plantar erythrodysesthesia syndrome.
Treatment-related events with incidence ≥5% in any group. Treatment-related grade 5 events included autoimmune hemolytic anemia, cardiac arrest, myocarditis, gastric hemorrhage (n = 2), gastric perforation (n = 3), gastric ulcer perforation, gastrointestinal hemorrhage, immune-mediated enterocolitis, intestinal ischemia, acute pancreatitis, upper gastrointestinal hemorrhage (n = 3), death, aseptic meningitis, sepsis, urosepsis, pulmonary embolism, intracranial hemorrhage, and malignant neoplasm progression and encephalitis in the lenvatinib plus pembrolizumab and chemotherapy group in one participant each unless otherwise indicated and gastrointestinal hemorrhage and hepatic failure in one participant each in the chemotherapy group.