Table 3.
Immune-related adverse events
| Trial | Treatment | Number of patients | Any irAE, n (%) | G3/G4 irAE, n (%) | Most common (G3/G4) | RC withheld because of TRAEs | Treatment discontinuation |
|---|---|---|---|---|---|---|---|
| ABACUS [53] | Atezolizumab | 87 | 6 (6.8) | 6 (6.8) | Hepatitis (4.5%)/skin rash (1.1%)/myocarditis (1.1%) | 3 (3.5%) | Yes (3%) |
| ABACUS-2 [19] | Atezolizumab | 23 | 3 (13) | 1 (4.3) | Hepatitis (9%)/kidney injury (4%) | No | No |
| ANTICIPATE [60] | Tislelizumab and APL-1202 (nitroxoline) | 9 | – | – | Hepatitis (11.1%) | – | No |
| ANTICIPATE II [61] | A: Tislelizumab and APL-1202 (nitroxoline) B: Tislelizumab |
32 total A: 18 B: 14 |
2 (11) 2 (14.3) |
– – |
Kidney injury (5.5%)/hepatitis (5.5%) Immune hyperthyroidism (14.3%) |
Yes Yes |
Yes (11.1%) Yes (7.2%) |
| AURA [42] | A: Avelumab + ddMVAC B: Avelumab + GC C: Avelumab + paclitaxel + gemcitabine D: Avelumab |
137 total A: 39 B: 40 C: 29 D: 29 |
– – – – |
– – – – |
– | 2 (1.4%) | – |
| BL-AIR [17] | Avelumab | 1 | 1 (100) | 0 | Kidney injury (100%) | – | Yes (100%) |
| BLASST-1 [16] | Nivolumab + GC | 41 | 28 (68) | 0 | Skin rash (30%)/hepatitis (27%)/kidney injury (7%) | No | No |
| BLASST-2 [18] | A: Durvalumab B: Durvalumab + oleclumab |
20 total A: 10 B: 10 |
– – |
– – |
– – |
– – |
No |
| ChiCTR2100050763 [13] | A: Cisplatin + gemcitabine + tislelizumab B: Carboplatin + gemcitabine + tislelizumab |
21 total | – – |
– – |
– | No No |
– |
| DUTRENEO [11] | A: Cold group—standard cisplatin-based CT (GC or ddMVAC) B: Hot group—standard cisplatin-based CT (GC or ddMVAC) C: Hot group—durvalumab + tremelimumab |
61 total A: 16 B: 22 C: 23 |
0 2 (12.5) 5 (21) |
0 1 (4.5) 1 (4.3) |
Absent Skin rash (4%) Skin rash (8%)/hepatitis (2%) |
1 (6%) 2 (9%) 3 (13%) |
No |
| HCRN GU14-188 [15] | A: GC + pembrolizumab B: Gemcitabine + pembrolizumab |
82 total A: 42 B: 40 |
– – |
10 (11.2) – – |
Hepatitis (3.7%)/skin rash (2.5%)/pneumonitis (2.5%)/colitis (2.5%) | – – |
– |
| HCRN GU16-257 | GC + nivolumab | 76 | 70 (92) | 1 (1.3) | Kidney injury (50%)/hepatitis (25%)/skin rash (17%) | – | – |
| LCCC1520 [32] | Pembrolizumab + GC | 39 | 1 (2.5) | 1 (2.5) | Diabetes mellitus (2.5%) | No | Yes (2%) |
| MDACC [10] | Durvalumab + tremelimumab | 28 | 30 (100) | 18 (64) | Skin rash (29%)/amylase increased (29%)/hepatitis (21%)/lipase increased (18%)/colitis (11%) | 2 (7%) | Yes (7%) |
| NABUCCO [31] | Nivolumab + ipilimumab | 24 | 24 (100) | 13 (54) | Lipase increased (33%)/diarrhea (21%)/hepatitis (21%)/skin rash (21%)/colitis (12%) | 1 (4%) | Yes (25%) |
| NCT00362713 [12] | Ipilimumab | 6 | – | – | – | – | – |
| NCT02989584 [54] | Atezolizumab + GC | 39 | 47 (100) | 7 (18) | Pancreatitis (9%)/hepatitis (2%)/kidney injury (2%)/skin rash (2%) | No | No |
| NCT03520491 [35] | A: Nivolumab B: Nivolumab + ipilimumab |
30 total A: 15 B: 15 |
– – |
– – |
Myocardites (1.7%) Lipase increase (20%)/hepatitis (33%) |
1 (6.6%) 2(13%) |
Yes (6.6%) Yes (13%) |
| NCT03912818 [57] | A: Durvalumab + ddMVAC B: Durvalumab + GC C: Durvalumab, carboplatin, and gemcitabine |
6 total A: 3 B: 0 C: 3 |
0 – 1 (33) |
0 – 0 |
Absent – Kidney injury (33%) |
No – No |
No – No |
| NCT04430036 [58] | AGEN1884 (anti–CTLA-4 antibody) + AGEN2034 (anti–PD-1) + GC | 4 | 2 (50) | 0 | Hepatitis (25%)/skin rash (25%) | No | No |
| NCT04610671 [59] | Nivolumab + CG0070 | 21 | 1(5) | 0 | Thyroiditis (5%) | No | No |
| NCT04861584 [34] | Toripalimab + GC | 16 | 5 (30) | 0 | Thyroiditis (18.75%)/skin rash (12.5%) | – | No |
| NEBULA [37] | A: Atezolizumab (single dose) B: Atezolizumab (2 doses) C: Atezolizumab (3 doses) |
20 total A: 6 B: 5 C: 9 |
2 (33) 1 (20) 6 (66) |
0 0 0 |
Kidney injury (33%) Skin rash (20%) Kidney injury (27%)/skin rash (18%)/hepatitis (9%) |
No No No |
No No No |
| NEMIO [41] | A: Durvalumab + ddMVAC B: Durvalumab, tremelimumab + ddMVAC |
120 total A: 60 B: 59 |
0 0 |
0 0 |
Absent Absent |
– – |
No No |
| NEODURVARIB [56] | Durvalumab + olaparib | 28 | – | – | – | – | – |
| NIAGARA [8] | A: Durvalumab + GC →durvalumab B: GC |
1063 total A: 533 B: 530 |
98 (18.5) 77 (14.6) |
11 (2) 4 (0.75) |
Kidney injury (18.5%) Kidney injury (14.6%) |
9 (1.7%) 6 (1.1%) |
Yes (21.1%) Yes (15.1%) |
| NURE-COMBO [39] | Nivolumab + nab-paclitaxel | 31 | 7 (22.6) | 1 (3.2) | Hepatitis (22.6%) | – | Yes (16.1%) |
| PANDORE [55] | Pembrolizumab | 39 | – | – | – | – | – |
| PIVOT IO 009 [29] |
A: Nivolumab + B B: Nivolumab C: Radical cystectomy |
114 total A: 37 B: 37 C: 40 |
10 (27) 10 (27) 0 |
– – 0 |
Kidney Injury (13.5%)/skin rash (10.81%)/amylase increased (5.4%) Kidney injury (10.81%)/skin rash (10.81%)/arthritis (5.4%)/0 |
– – – |
Yes (21.6%) Yes (21.6%) No |
| PrECOG PrE0807 [38] | A: Nivolumab B: Nivolumab and lirilumab |
43 total A: 13 B: 30 |
1 (8) 3 (10) |
0 0 |
Skin rash (8%) Skin rash (10%) |
No No |
No No |
| PURE-01 [36] | Pembrolizumab | 155 | 11 (7.1) | 2 (1.2) | Hepatitis (3.9%)/skin rash (3.2%) | No | No |
| SAKK 06/17 [40] | Durvalumab + cisplatin-gemcitabine | 58 | 29 (50) | 7 (12) | Hepatitis (14%)/diarrhea (12%)/lipase or amylase increased (11%) | No | No |
| SunRise-4 [62] | A: TAR-200 (intravesical gradual release of gemcitabine) and cetrelimab B: Cetrelimab |
122 total A: 80 B: 42 |
– – |
– – |
– – |
No No |
Yes (8.9%) Yes (7.6%) |
| TRUCE-01 [33] | Tislelizumab + nab-paclitaxel | 47 | 26 (55) | 4 (8.4) | Skin rash (41%)/kidney injury (14%) | – | Yes (6.3%) |
B = bempegaldesleukin; CT = chemotherapy; CTLA-4 = T-lymphocyte–associated protein 4; ddMVAC = dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin; G = grade; GC = cisplatin + gemcitabine; irAE = immune-related adverse event; PD-1 = programmed cell death protein 1; RC = radical cystectomy; TRAE = treatment-related adverse event.