TABLE 3.
List of the studies involving serious AEs in this meta-analysis.
| First author | Year | NCT number | Trail name | Total number | Cancer type | Trial phase | Treatment | Patient number | Total number surveyed | Grade 3 or higher AEs |
|---|---|---|---|---|---|---|---|---|---|---|
| Fehrenbacher L et al. (Fehrenbacher et al., 2016) | 2016 | NCT01903993 | POPLAR | 287 | Non small cell lung cancer | 2 | Atezolizumab | 144 | 142 | 17 |
| 2 | Standard | 143 | 135 | 55 | ||||||
| Fehrenbacher L et al. (Fehrenbacher et al., 2018) | 2018 | NCT02008227 | OAK | 1225 | Non small cell lung cancer | 3 | Atezolizumab | 613 | 609 | 91 |
| 3 | Standard | 612 | 578 | 246 | ||||||
| McDermott DF et al. (McDermott et al., 2018) | 2018 | NCT01984242 | IMmotion150 | 204 | Renal cell carcinoma | 2 | Atezolizumab | 103 | 103 | 17 |
| 2 | Standard | 101 | 100 | 57 | ||||||
| Powles T et al. (Powles et al., 2018) | 2018 | NCT02302807 | IMvigor211 | 234 | Urothelial carcinoma | 3 | Atezolizumab | 116 | 114 | 11 |
| 3 | Standard | 118 | 112 | 43 | ||||||
| Eng C et al. (Eng et al., 2019) | 2019 | NCT02788279 | IMblaze370 | 180 | Colorectal cancer | 3 | Atezolizumab | 90 | 90 | 28 |
| 3 | Standard | 90 | 80 | 46 | ||||||
| Herbst RS et al. (Herbst et al., 2020) | 2020 | NCT02409342 | IMpower110 | 554 | Non small cell lung cancer | 3 | Atezolizumab | 277 | 286 | 97 |
| 3 | Standard | 277 | 263 | 149 | ||||||
| Bang YJ et al. (Bang et al., 2018) | 2018 | NCT02625623 | JAVELIN Gastric 300 | 371 | Gastric/gastrooesophageal junction cancer | 3 | Avelumab | 185 | 184 | 17 |
| 3 | Standard | 186 | 177 | 56 | ||||||
| Park K et al. (Park et al., 2021) | 2021 | NCT02395172 | JAVELIN Lung 200 | 529 | Non small cell lung cancer | 3 | Avelumab | 264 | 393 | 41 |
| 3 | Standard | 265 | 365 | 180 | ||||||
| Pujade-Lauraine E et al. (Pujade-Lauraine et al., 2021) | 2021 | NCT02580058 | JAVELIN Ovarian 200 | 378 | Ovarian cancer | 3 | Avelumab | 188 | 187 | 30 |
| 3 | Standard | 190 | 177 | 56 | ||||||
| Huang J et al. (Huang et al., 2020) | 2020 | NCT03099382 | ESCORT | 448 | Squamous cell carcinoma | 3 | Camrelizumab | 228 | 228 | 44 |
| 3 | Standard | 220 | 220 | 87 | ||||||
| Sezer A et al. (Sezer et al., 2021) | 2021 | NCT03088540 | EMPOWER-Lung 1 | 563 | Non small cell lung cancer | 3 | Cemiplimab | 283 | 355 | 50 |
| 3 | Standard | 280 | 342 | 134 | ||||||
| O'Reilly EM et al. (O'Reilly et al., 2019) | 2019 | NCT02558894 | NA | 65 | Pancreatic ductal adenocarcinoma | 2 | Durvalumab+Tremelimumab | 32 | 32 | 7 |
| 2 | Durvalumab | 33 | 32 | 2 | ||||||
| Siu LL et al. (Siu et al., 2019) | 2019 | NCT02319044 | CONDOR | 267 | Squamous Cell Carcinoma | 2 | Durvalumab+Tremelimumab | 133 | 133 | 21 |
| 2 | Durvalumab | 67 | 65 | 8 | ||||||
| 2 | Tremelimumab | 67 | 65 | 11 | ||||||
| Ferris RL et al. (Ferris et al., 2020) | 2020 | NCT02369874 | EAGLE | 736 | Squamous cell carcinoma | 3 | Durvalumab | 240 | 237 | 24 |
| 3 | Durvalumab+Tremelimumab | 247 | 246 | 40 | ||||||
| 3 | Standard | 249 | 240 | 58 | ||||||
| Planchard D et al. (Planchard et al., 2020) | 2020 | NCT02352948 | ARCTIC | 595 | Non small cell lung cancer | 3 | Durvalumab | 62 | 62 | 6 |
| 3 | Durvalumab+Tremelimumab | 174 | 173 | 38 | ||||||
| 3 | Durvalumab | 117 | 117 | 14 | ||||||
| 3 | Tremelimumab | 60 | 60 | 14 | ||||||
| 3 | Standard | 64 | 63 | 28 | ||||||
| 3 | Standard | 118 | 110 | 40 | ||||||
| Powles T et al. (Powles et al., 2020) | 2020 | NCT02516241 | DANUBE | 1032 | Urothelial carcinoma | 3 | Durvalumab | 346 | 345 | 49 |
| 3 | Durvalumab+Tremelimumab | 342 | 340 | 95 | ||||||
| 3 | Standard | 344 | 313 | 189 | ||||||
| Rizvi NA et al. (Rizvi et al., 2020) | 2020 | NCT02453282 | MYSTIC | 488 | Non small cell lung cancer | 3 | Durvalumab | 163 | 369 | 55 |
| 3 | Durvalumab+Tremelimumab | 163 | 371 | 85 | ||||||
| 3 | Standard | 162 | 352 | 119 | ||||||
| Bachelot T et al. (Bachelot et al., 2021) | 2021 | NCT02299999 | SAFIR02-BREAST IMMUNO | 199 | Breast cancer | 2 | Durvalumab | 68 | 63 | 10 |
| 2 | Standard | 131 | 129 | 17 | ||||||
| Hodi FS et al. (Hodi et al., 2010) | 2010 | NCT00094653 | MDX010-20 | 273 | Melanoma | 3 | Ipilimumab | 137 | 131 | 30 |
| 3 | Standard | 136 | 132 | 15 | ||||||
| Bang YJ et al. (Bang et al., 2017) | 2017 | NCT01585987 | NA | 108 | Gastric/gastrooesophageal junction cancer | 2 | Ipilimumab | 57 | 57 | 13 |
| 2 | Standard | 51 | 45 | 4 | ||||||
| Borghaei H et al. (Borghaei et al., 2015) | 2015 | NCT01673867 | CheckMate 057 | 582 | Non small cell lung cancer | 3 | Nivolumab | 292 | 287 | 30 |
| 3 | Standard | 290 | 268 | 144 | ||||||
| Brahmer J et al. (Brahmer et al., 2015) | 2015 | NCT01642004 | CheckMate 017 | 272 | Non small cell lung cancer | 3 | Nivolumab | 135 | 131 | 9 |
| 3 | Standard | 137 | 129 | 71 | ||||||
| Motzer RJ et al. (Motzer et al., 2015) | 2015 | NCT01668784 | CheckMate 025 | 821 | Renal cell carcinoma | 3 | Nivolumab | 410 | 406 | 76 |
| 3 | Standard | 411 | 397 | 145 | ||||||
| Ferris RL et al. (Ferris et al., 2016) | 2016 | NCT02105636 | CheckMate 141 | 361 | Squamous cell carcinoma | 3 | Nivolumab | 240 | 236 | 31 |
| 3 | Standard | 121 | 111 | 39 | ||||||
| Hodi FS et al. (Hodi et al., 2016) | 2016 | NCT01927419 | CheckMate 069 | 142 | Melanoma | 2 | Nivolumab+Ipilimumab | 95 | 94 | 51 |
| 2 | Ipilimumab | 47 | 46 | 9 | ||||||
| Carbone DP et al. (Carbone et al., 2017) | 2017 | NCT02041533 | CheckMate 026 | 541 | Non small cell lung cancer | 3 | Nivolumab | 271 | 267 | 47 |
| 3 | Standard | 270 | 263 | 133 | ||||||
| Weber J et al. (Weber et al., 2017) | 2017 | NCT02388906 | CheckMate 238 | 906 | Melanoma | 3 | Nivolumab | 453 | 452 | 65 |
| 3 | Ipilimumab | 453 | 453 | 208 | ||||||
| Amaria RN et al. (Amaria et al., 2018) | 2018 | NCT02519322 | NA | 23 | Melanoma | 2 | Nivolumab | 12 | 12 | 1 |
| 2 | Nivolumab+Ipilimumab | 11 | 11 | 8 | ||||||
| Hodi FS et al. (Hodi et al., 2018) | 2018 | NCT01844505 | CheckMate 067 | 945 | Melanoma | 3 | Nivolumab+Ipilimumab | 314 | 313 | 185 |
| 3 | Ipilimumab | 315 | 311 | 86 | ||||||
| 3 | Nivolumab | 316 | 313 | 70 | ||||||
| Larkin J et al. (Larkin et al., 2018) | 2018 | NCT01721746 | CheckMate 037 | 405 | Melanoma | 3 | Nivolumab | 272 | 268 | 37 |
| 3 | Standard | 133 | 102 | 84 | ||||||
| Ascierto PA et al. (Ascierto et al., 2019) | 2019 | NCT01721772 | CheckMate 066 | 418 | Melanoma | 3 | Nivolumab | 210 | 206 | 31 |
| 3 | Standard | 208 | 205 | 36 | ||||||
| Hellmann MD et al. (Hellmann et al., 2019) | 2019 | NCT02477826 | CheckMate 227 | 1166 | Non small cell lung cancer | 3 | Nivolumab+Ipilimumab | 583 | 576 | 189 |
| 3 | Standard | 583 | 570 | 205 | ||||||
| Kato K et al. (Kato et al., 2019) | 2019 | NCT02569242 | ATTRACTION-3 | 419 | Squamous cell carcinoma | 3 | Nivolumab | 210 | 209 | 38 |
| 3 | Standard | 209 | 208 | 133 | ||||||
| Scherpereel A et al. (Scherpereel et al., 2019) | 2019 | NCT02716272 | IFCT-1501 MAPS2 | 125 | Malignant pleural mesothelioma | 2 | Nivolumab | 63 | 63 | 9 |
| 2 | Nivolumab+Ipilimumab | 62 | 61 | 16 | ||||||
| Wu YL et al. (Wu et al., 2019) | 2019 | NCT02613507 | CheckMate 078 | 504 | Non small cell lung cancer | 3 | Nivolumab | 338 | 337 | 35 |
| 3 | Standard | 166 | 156 | 74 | ||||||
| Motzer RJ et al. (Motzer et al., 2020) | 2020 | NCT02231749 | CheckMate 214 | 1096 | Renal cell carcinoma | 3 | Nivolumab+Ipilimumab | 550 | 547 | 259 |
| 3 | Standard | 546 | 535 | 343 | ||||||
| Reardon DA et al. (Reardon et al., 2020) | 2020 | NCT02017717 | CheckMate 143 | 369 | Glioblastoma | 3 | Nivolumab | 184 | 182 | 33 |
| 3 | Standard | 185 | 165 | 25 | ||||||
| Zimmer L et al. (Zimmer et al., 2020) | 2020 | NCT02523313 | IMMUNED | 115 | Melanoma | 2 | Nivolumab+Ipilimumab | 56 | 55 | 39 |
| 2 | Nivolumab | 59 | 56 | 15 | ||||||
| Baas P et al. (Baas et al., 2021) | 2021 | NCT02899299 | CheckMate 743 | 605 | Malignant pleural mesothelioma | 3 | Nivolumab+Ipilimumab | 303 | 300 | 91 |
| 3 | Standard | 302 | 284 | 91 | ||||||
| Owonikoko TK et al. (Owonikoko et al., 2021) | 2021 | NCT02538666 | CheckMate 451 | 559 | Small cell lung cancer | 3 | Nivolumab+Ipilimumab | 279 | 278 | 145 |
| 3 | Nivolumab | 280 | 279 | 32 | ||||||
| Spigel DR et al. (Spigel et al., 2021) | 2021 | NCT02481830 | CheckMate 331 | 569 | Small cell lung cancer | 3 | Nivolumab | 284 | 282 | 39 |
| 3 | Standard | 285 | 265 | 194 | ||||||
| Tannir NM et al. (Tannir et al., 2021) | 2021 | NA | CheckMate 214 | 139 | Renal cell carcinoma | 3 | Nivolumab+Ipilimumab | 74 | 73 | 36 |
| 3 | Standard | 65 | 65 | 29 | ||||||
| Ribas A et al. (Ribas et al., 2013) | 2013 | NCT00257205 | NA | 655 | Melanoma | 3 | Tremelimumab | 328 | 325 | 192 |
| 3 | Standard | 327 | 319 | 132 | ||||||
| Herbst RS et al. (Herbst et al., 2016) | 2016 | NCT01905657 | KEYNOTE-010 | 687 | Non small cell lung cancer | 2/3 | Pembrolizumab | 344 | 339 | 43 |
| 2/3 | Standard | 343 | 309 | 109 | ||||||
| Hamid O et al. (Hamid et al., 2017) | 2017 | NCT01704287 | KEYNOTE-002 | 359 | Melanoma | 2 | Pembrolizumab | 180 | 178 | 24 |
| 2 | Standard | 179 | 171 | 45 | ||||||
| Shitara K et al. (Shitara et al., 2018) | 2018 | NCT02370498 | KEYNOTE-061 | 395 | Gastric/gastrooesophageal junction cancer | 3 | Pembrolizumab | 196 | 294 | 42 |
| 3 | Standard | 199 | 276 | 96 | ||||||
| Cohen EEW et al. (Cohen et al., 2019) | 2019 | NCT02252042 | KEYNOTE-040 | 495 | Squamous cell carcinoma | 3 | Pembrolizumab | 247 | 246 | 33 |
| 3 | Standard | 248 | 234 | 85 | ||||||
| Fradet Y et al. (Fradet et al., 2019) | 2019 | NCT02256436 | KEYNOTE-045 | 542 | Urothelial cancer | 3 | Pembrolizumab | 270 | 266 | 44 |
| 3 | Standard | 272 | 255 | 128 | ||||||
| Mok TSK et al. (Mok et al., 2019) | 2019 | NCT02220894 | KEYNOTE-042 | 1274 | Non-small cell lung cancer | 3 | Pembrolizumab | 637 | 636 | 113 |
| 3 | Standard | 637 | 615 | 252 | ||||||
| Reck M et al. (Reck et al., 2019) | 2019 | NCT02142738 | KEYNOTE-024 | 305 | Non-small cell lung cancer | 3 | Pembrolizumab | 154 | 154 | 48 |
| 3 | Standard | 151 | 150 | 80 | ||||||
| Robert C et al. (Robert et al., 2019) | 2019 | NCT01866319 | KEYNOTE-006 | 834 | Melanoma | 3 | Pembrolizumab | 556 | 555 | 103 |
| 3 | Ipilimumab | 278 | 256 | 54 | ||||||
| André T et al. (André et al., 2020) | 2020 | NCT02563002 | KEYNOTE-177 | 307 | Colorectal cancer | 3 | Pembrolizumab | 153 | 153 | 86 |
| 3 | Standard | 154 | 143 | 111 | ||||||
| Kojima T et al. (Kojima et al., 2020) | 2020 | NCT02564263 | KEYNOTE-181 | 628 | Esophageal cancer | 3 | Pembrolizumab | 314 | 314 | 57 |
| 3 | Standard | 314 | 296 | 121 | ||||||
| Popat S et al. (Popat et al., 2020) | 2020 | NCT02991482 | ETOP 9-15 | 144 | Malignant pleural mesothelioma | 3 | Pembrolizumab | 73 | 72 | 14 |
| 3 | Standard | 71 | 70 | 18 | ||||||
| Kuruvilla J et al. (Kuruvilla et al., 2021) | 2021 | NCT02684292 | KEYNOTE-204 | 304 | Hodgkin lymphoma | 3 | Pembrolizumab | 151 | 148 | 29 |
| 3 | Standard | 153 | 152 | 38 |
AEs = Adverse events.