Table 2.
Grade ≥3 AEs that were reported in patients included in trials comparing combination therapy vs. sunitinib in first-line treatment for advanced renal cell carcinoma.
| CheckMate 9ER | CheckMate 214 | Javelin101 | Keynote426 | CLEAR | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Events | NIVO + CABO | SUN | NIVO+ | SUN | AVELU + AXI | SUN | PEMBRO + AXI | SUN | LEN + PEMBRO | SUN |
| (%) | IPI | |||||||||
| N = 320 | N = 320 | N = 547 | N = 535 | N = 434 | N = 439 | N = 429 | N = 425 | N = 352 | N = 340 | |
| Treatment-related AEs | 61% | 51% | 47.3% | 64.1% | 71.2% | 71.5% | 67% | 62% | 71.6% | 58.8% |
| Diarrhea | 6.9% | 4.4% | 3.8% | 5.8% | 6.7% | 2.7% | 10.7% | 5% | 9.7% | 5.3% |
| Nausea | 0.6% | 0.3% | 1.5% | 1.3% | 1.4% | 1.6% | 0.5% | 0.9% | 2.6% | 0.6% |
| Stomatitis | 2.5% | 2.2% | 0% | 2.6% | 1.8% | 0.9% | 1% | 2.1% | 1.7% | 2.1% |
| Mucosal inflammation | 0.9% | 2.5% | 0.2% | 2.8% | 1.2% | 1.1% | 0.9% | 1.6% | NR | NR |
| Increased lipase | 6.2% | 4.7% | 10.6% | 6.7% | NR | NR | NR | NR | 12.8% | 8.8% |
| Decreased appetite | 1.9% | 1.2% | 1.3% | 1.1% | 2.1% | 0.9% | 2.1% | 0.5% | 4.0% | 1.5% |
| Decreased weight | 0.6% | 0% | NR | NR | 2.8% | 0.9% | 3.0% | 0.2% | 8.0% | 0.3% |
| Back pain | 1.6% | 1.9% | NR | NR | 0.5% | 1.8% | 0.9% | 1.6% | 1.1% | 2.1% |
| Asthenia | 4.4% | 3.1% | 1.8% | 2.4% | 2.5% | 3.0% | 1.4% | 3% | 4.5% | 3.2% |
| Vomiting | 1.9% | 0.3% | 0.7% | 1.9% | 0.9% | 1.6% | 0.2% | 1% | 3.4% | 1.5% |
| Dyspnea | NR | NR | NR | NR | 3.0% | 1.6% | 1.6% | 1.2% | 2.6% | 2.4% |
| Fatigue | 3.4% | 4.7% | 4.4% | 9.7% | 3.5% | 3.6% | 3% | 5% | 4.3% | 4.4% |
| Arthralgia | 0.3% | 0.3% | NR | NR | 0.9% | 0.5% | 0.7% | 0.5% | 1.4% | 0.3% |
| Rash | 1.9% | 0% | 1.6% | 0% | 0.5% | 0.5% | 0.2% | 0.2% | 3.7% | 0.6% |
| Hypertension | 12.5% | 13.1% | 0.7% | 17.0% | 25.6% | 17.1% | 22% | 20% | 27.6% | 18.8% |
| Palmoplantar erythrodysesthesia | 7.5% | 7.5% | 0.2% | 9.3% | 5.8% | 4.3% | 0.5% | 5% | 4.0% | 3.8% |
| Anemia | 1.9% | 3.8% | 0.5% | 4.3% | 1.6% | 8.2% | 0.2% | 4.0% | 2.0% | 5.3% |
| Thrombocytopenia | 0.6% | 4.7% | 0% | 4.3% | 0.2% | 6.2% | 0% | 5.2% | 0.6% | 5.6% |
| AST increased | 3.4% | 1.2% | NR | NR | 3.9% | 2.1% | 6.8% | 1.6% | 3.1% | 0.9% |
| ALT increased | 5.3% | 2.2% | NR | NR | 6.0% | 2.5% | 13% | 2.6% | 4.3% | 2.4% |
| Proteinuria | 2.8% | 2.2% | NR | NR | NR | NR | 3% | 3% | 7.7% | 2.9% |
| Treatment-related AE leading to discontinuation | NR | NR | 15.4% | 7.3% | 7.6% | 13.4% | 18.2% | 16.2% | NR | NR |
| Treatment-related deaths | 1% a | 2% b | NR | NR | 0.3% c | 0.2% d | 0.9% e | 1.6% f | NR | NR |
NIVO: nivolumab; CABO: cabozantinib; SUN: sunitinib; IPI: ipilimumab; AVELU: avelumab; AXI: axitinib; PEMBRO: pembrolizumab; AE: adverse event. N: total number of patients with available safety data information. Includes events reported between the first dose and 30 days after the last dose of the studied therapy. Listed are grade ≥3 AEs that were reported in >1% of the patients in either arm. a Small intestine perforation; b pneumonia, respiratory distress; c intervention group was attributed to sudden death, myocarditis, and necrotizing pancreatitis; d intestinal perforation; e one patient each with myasthenia gravis, myocarditis, necrotizing fasciitis, and pneumonitis; f one patient each with acute myocardial infarction, cardiac arrest, gastrointestinal hemorrhage, hemorrhage intracranial, hepatitis fulminant, malignant neoplasm progression, and pneumonia.