Table 3 Immune-related toxicity data reported in front-line combinations with ICIs in advanced RCC Clinical Trials
| CheckMate 214 Nivolumab + Ipilimumab (NCT02231749) [9] (n = 547) | Keynote-426 Pembrolizumab + Axitinib (NCT02853331) [11] (n = 429) | Javelin RENAL 101 Avelumab + Axitinib (NCT02684006) [12, 13] (n = 434) | IMmotion151 Atezolizumab + Bevacizumab (NCT02420821) [14] (n = 451) | CheckMate 025 Nivolumab (NCT01668784) [16] (n = 406) | ||
|---|---|---|---|---|---|---|
| Number of patients (%) | ||||||
| Total Events | Any TRAE | 509 (93) | 422 (98.4) | 432 (95.4) | 411 (91) | 319 (79) |
| Grade 3–4 TRAEs | 250 (46) | 270 (63) | 309 (56.7) | 182 (40) | 76 (19) | |
| TRAEs leading to discontinuation of either drug | – | 131 (30.5) | – | Atezolizumab: 9 (2); Bevacizumab: 23 (5) | 31 (8) | |
| TRAEs leading to discontinuation of both drugs | 118 (22) | 45 (10.7) | 33 (7.6) | 24 (5) | – | |
| Treatment related deaths | 8 (1.5) | 4 (0.9) | 3 (0.7) | 5 (1.1) | 0 | |
| Most Common AEs (Any Grade) | Fatigue | 202 (37) | 165 (38.5) | 180 (41.5) | 134 (33) | |
| Pruritus | 154 (28) | 61 (14.1) | 57 (14) | |||
| Diarrhea | 145 (27) | 233 (54.3) | 270 (62.2) | 50 (12) | ||
| Hypertension | 12 (2) | 191 (44.5) | 215 (49.5) | – | ||
| Rash | 118 (22) | 61 (14.2) | 62 (14.3) | 41 (10) | ||
| Nausea | 109 (20) | 119 (27.7) | 148 (34.1) | 57 (14) | ||
| Increased lipase | 90 (16) | – | – | – | ||
| Hypothyroidism | 85 (16) | 152 (35.4) | 108 (24.9) | – | ||
| Palmar-plantar erythrodysesthesia | 5 (< 1) | 120 (28.0) | 145 (33.4) | – | ||
| Most Common TRAEs (Grade 3–4) | Fatigue | 23 (4) | 12 (2.8) | 15 (3.5) | 10 (2) | |
| Diarrhea | 21 (4) | 39 (9.1) | 29 (6.7) | 5 (1) | ||
| Hypertension | 4 (< 1) | 95 (22.1) | 111 (25.6) | 63 (14) | – | |
| Increased lipase | 56 (10) | – | – | – | ||
| Palmar-plantar erythrodysesthesia | 0 | 22 (5.1) | 25 (5.8) | – | ||
| Alanine aminotransferase increased | – | 57 (13.3) | 26 (6.0) | – | ||
| Aspartate aminotransferase increased | – | 30 (7.0) | 17 (3.9) | – | ||