Table 2.
Summary of safety data reported by eligible studies in the network
| Study | Treatment arm | Population | N analysed | All-grade TRAEs, n (%) | Grade 3–4 TRAEs, n (%) | All-grade TRSAEs, n (%) | Death due to AEs, n (%) | Treatment discontinuation due to AEs, n (%) |
|---|---|---|---|---|---|---|---|---|
| Yau et al. [28] 2022 CheckMate 459 | Nivolumab | ITT | 367 | 257 (70) | 81 (22.1) | 43 (11.7) | 4 (1.1) | 27 (7.4) |
| Sorafenib | ITT | 363 | 338 (93.1) | 179 (49.3) | 39 (10.7) | 1 (0.28) | 42 (11.6) | |
| Kelley et al. [29] 2022 COSMIC-312 | Cabozantinib plus atezolizumab | ITT | 429 | 399 (93) | 273 (63.6) | 78 (18) | 51 (12) | Led to discontinuation, any treatment: 58 (14) |
| Led to discontinuation, both treatments: 26 (6) | ||||||||
| Sorafenib | ITT | 207 | 186 (90) | 95 (45.9) | 16 (8) | 23 (11) | 16 (8) | |
| Cabozantinib | ITT | 188 | 178 (95) | 113 (60.1) | 24 (13) | 30 (16) | 16 (9) | |
| Abou-Alfa et al. [17] 2022 HIMALAYA | STRIDE | ITT | 388 | 294 (75.8) | 100 (25.8) | 68 (17.5) | 9 (2.3) | 32 (8.2) |
| Durvalumab | ITT | 388 | 202 (52.1) | 50 (12.9) | 32 (8.2) | 0 (0) | 16 (4.1) | |
| Sorafenib | ITT | 374 | 317 (84.8) | 138 (36.9) | 35 (9.4) | 3 (0.8) | 41 (11) | |
| T75 + durvalumab | ITT | 152 | 106 (69.7) | 32 (21.2) | 28 (18.4) | 2 (1.3) | 13 (8.6) | |
| Finn et al. [8, 30] 2020 IMbrave150 | Atezolizumab plus bevacizumab | Rest of ITT population (non-Vp4) | 285 | 247 (87) | 125 (44) | 65 (23) | 5 (2) | Led to discontinuation, any treatment: 61 (21) |
| Sorafenib | Rest of ITT population (non-Vp4) | 133 | 126 (95) | 61 (46) | 20 (15) | 1 (1) | Led to discontinuation, any treatment: 16 (12) | |
| Finn et al. [31] 2022 LEAP-002 | Lenvatinib plus pembrolizumab | ITT | 395 | 381 (96.5) | 243 (61.5) | NR | 4 (1.0) | Led to discontinuation, any treatment: 71 (18) |
| Led to discontinuation, both treatments: 22 (5.6) | ||||||||
| Lenvatinib plus placebo | ITT | 395 | 378 (95.7) | 224 (56.7) | NR | 3 (0.8) | Led to discontinuation, any treatment: 42 (10.6) | |
| Led to discontinuation, both treatments: 18 (4.6) | ||||||||
| Qin et al. [32] 2022, NCT03764293 | Camrelizumab plus rivoceranib | ITT | 272 | 265 (97.4) | 219 (80.5) | 66 (24.3) | 1 (0.4) | Discontinuation of any treatment components: 66 (24.3) |
| Discontinuation of all treatment components: 10 (3.7) | ||||||||
| Sorafenib | ITT | 269 | 249 (92.6) | 140 (52) | 16 (5.9) | 1 (0.4) | Discontinuation of any treatment components: 12 (4.5) | |
| Discontinuation of all treatment components: 12 (4.5) | ||||||||
| Qin et al. [19] 2022 RATIONALE-301 | Tislelizumab | ITT | 338 | 259 (76.6) | NR | 40 (11.8) | 3 (0.9) | 37 (10.9) |
| Sorafenib | ITT | 324 | 311 (96) | NR | 33 (10.2) | 2 (0.6) | 60 (18.5) | |
| Kudo et al. [7] 2018 REFLECT | Lenvatinib | ITT | 476 | 447 (94) | NR | 84 (18) | 11 (2) | 63 (13.2) |
| Sorafenib | ITT | 475 | 452 (95) | NR | 48 (10) | 4 (1) | 43 (9.1) |
AE, adverse event; ITT, intent to treat; NR, not reported; STRIDE, 300 mg of tremelimumab for one dose plus 1,500 mg of durvalumab every 4 weeks; T75, 75 mg of tremelimumab every 4 weeks for four doses; TRAE, treatment-related adverse event; TRSAE, treatment-related serious adverse event.