Table 1.
List of randomized controlled trials analyzed in this meta-analysis
| First Author | Year | Study | Cancer | Cancer status | Study setting | ICI added | Control arm | Analyzed hepatotoxicity | Patients | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| ICI | Control | Ref. | |||||||||
| Bajorin DF | 2021 | CheckMate 274 | Urothelial | Muscle-invasive | Adjuvant | Nivolumab | Placebo | Hepatitis, AST, ALT | 351 | 348 | [27] |
| Bellmunt J | 2021 | IMvigor 010 | Urothelial | Muscle-invasive | Adjuvant | Atezolizumab | Observation | Hepatitis, AST, ALT | 390 | 397 | [28] |
| Boyer M | 2021 | KEYNOTE 598 | NSCLC | Metastatic | 1st line | Ipilimumab | Placebo + pembrolizumab | Hepatitis, AST, ALT | 282 | 281 | [29] |
| Cortes J | 2020 | KEYNOTE 355 | Breast | Advanced | 1st line | Pembrolizumab | GEM/PTX/nab-PTX + CBDCA | ALT | 562 | 281 | [30] |
| Di Giacomo AM | 2021 | NIBIT-M2 | Melanoma | Brain metastasis | 1st line | Ipilimumab | Fotemustine | AST, ALT | 26 | 27 | [31] |
| Eggermont AMM | 2016 | EORTC 18,071 | Melanoma | Resected Stage III | Adjuvant | Ipilimumab | Placebo | AST, ALT | 471 | 474 | [32] |
| Eggermont AMM | 2018 | KEYNOTE 054 | Melanoma | Resected Stage III | Adjuvant | Pembrolizumab | Placebo | Hepatitis | 509 | 502 | [33] |
| Ferris RL | 2020 | EAGLE | Head and Neck | Recurrent or metastatic | 2nd line | Tremelimumab | Durvalumab | ALT | 247 | 240 | [34] |
| Finn RS | 2020 | KEYNOTE 240 | HCC | Advanced | 2nd line | Pembrolizumab | Placebo + BSC | Hepatitis, AST, ALT | 279 | 134 | [35] |
| Galsky MD | 2020 | IMvigor 130 | Urothelial | Metastatic | 1st line | Atezolizumab | Placebo + GEM + CDDP/CBDCA | Hepatitis | 453 | 390 | [36] |
| Govindan R | 2017 | Study 104 | NSCLC | Advanced | 1st line | Ipilimumab | Placebo + CBDCA + PTX | AST, ALT | 388 | 361 | [37] |
| Gutzmer R | 2020 | IMspire 150 | Melanoma | Advanced | 1st line | Atezolizumab | Placebo + Vemurafenib + Cobimetinib | AST, ALT | 230 | 281 | [38] |
| Hodi FS | 2010 | MDX010-20 | Melanoma | Metastatic | 2nd or later line | Ipilimumab | gp100 | Hepatitis, AST, ALT | 380 | 132 | [39] |
| Hodi FS | 2018 | CheckMate 067 | Melanoma | Advanced | 1st line | Ipilimumab | Placebo + Nivolumab | Hepatitis, AST, ALT | 313 | 313 | [40] |
| Horn L | 2018 | IMpower 133 | SCLC | Metastatic | 1st line | Atezolizumab | Placebo + CBDCA + VP-16 | Hepatitis | 198 | 196 | [41] |
| Janjigian YY | 2021 | CheckMate 649 | GEJ | Advanced | 1st line | Nivolumab | CAPOX/FOLFOX | AST, ALT | 782 | 767 | [42] |
| Jotte R | 2020 | IMpower 131 | NSCLC | Advanced | 1st line | Atezolizumab | CBDCA + nabPTX | Hepatitis | 343 | 340 | [43] |
| Kang YK | 2017 | ATTRACTION-2 | Gastric | Advanced | 3rd or later line | Nivolumab | Placebo | Hepatitis, AST, ALT | 330 | 161 | [44] |
| Kelly RJ | 2021 | CheckMate 577 | GEJ | Resected stage II-III | Adjuvant | Nivolumab | Placebo | AST | 532 | 260 | [45] |
| Kwon ED | 2014 | CA184-043 | Prostate | mCRPC | 2nd line | Ipilimumab | Placebo following radiotherapy | Hepatitis, AST, ALT | 393 | 396 | [46] |
| Lee NY | 2021 | JAVELIN Head and Neck | Head and Neck | Locally-advanced | Definitive CRT | Avelumab | Placebo + CRT | Hepatitis, AST, ALT | 348 | 344 | [47] |
| Miles D | 2021 | IMpassion 131 | Breast | Advanced | 1st line | Atezolizumab | Placebo + PTX | Hepatitis, AST, ALT | 432 | 217 | [48] |
| Mittendorf EA | 2020 | IMpassion 031 | Breast | Stage II–III | Adjuvant | Atezolizumab | Placebo + nabPTX—> ADR + CPA | Hepatitis, AST, ALT | 164 | 167 | [49] |
| Moore KN | 2021 | IMagyn 050 | Ovarian | Stage III–IV | 1st line | Atezolizumab | Placebo + PTX + CBDCA + Bevacizumab | Hepatitis | 644 | 642 | [50] |
| Nishio M | 2020 | IMpower 132 | NSCLC | Stage IV | 1st line | Atezolizumab | CDDP/CBDCA + PEM | Hepatitis | 291 | 274 | [51] |
| Paz-Ares L | 2018 | KEYNOTE 407 | NSCLC | Metastatic | 1st line | Pembrolizumab | Placebo + CBDCA + PTX/nabPTX | Hepatitis | 278 | 280 | [13] |
| Paz-Ares L | 2019 | CASPIAN* | SCLC | Extended | 1st line | Durvalumab | CDDP/CBDCA + VP-16 | Hepatitis, AST**, ALT** | 265 | 266 | [52, 53] |
| Planchard D | 2020 | ARCTIC | NSCLC | Metastatic | 3rd or later line | Tremelimumab | Durvalumab | Hepatitis, AST, ALT | 173 | 117 | [54] |
| Powles T1 | 2020 | DANUBE | Urothelial | Advanced | 1st line | Tremelimumab | Durvalumab | Hepatitis, AST, ALT | 340 | 345 | [55] |
| Powles T2 | 2020 | JAVELIN Bladder 100 | Bladder | Advanced | 1st line (maintenance) | Avelumab | GEM + CDDP/CBDCA—> BSC | Hepatitis, AST, ALT | 350 | 350 | [56] |
| Powles T | 2021 | KEYNOTE 361 | Urothelial | Advanced | 1st line | Pembrolizumab | CDDP/CBDCA + GEM | Hepatitis, AST, ALT | 349 | 342 | [57] |
| Pujade-Lauraine E | 2021 | JAVELIN Ovarian 200 | Ovarian | Advanced | 2nd or later line | Avelumab | PLD | Hepatitis, AST, ALT | 182 | 177 | [58] |
| Reck M | 2016 | CA184-156 | SCLC | Extended | 1st line | Ipilimumab | CDDP/CBDCA + VP-16 | AST, ALT | 478 | 476 | [59] |
| Rizvi NA | 2020 | MYSTIC | NSCLC | Metastatic | 1st line | Tremelimumab | Durvalumab | Hepatitis | 372 | 374 | [60] |
| Robert C | 2011 | CA184-024 | Melanoma | Advanced | 1st line | Ipilimumab | Dacarbazine | Hepatitis, AST, ALT | 247 | 251 | [61] |
| Rodriguez-Abreu D | 2021 | KEYNOTE 189* | NSCLC | Metastatic | 1st line | Pembrolizumab | Placebo + CDDP/CDBCA + PEM | Hepatitis, ALT*** | 405 | 202 | [62, 63] |
| Rudin CM | 2020 | KEYNOTE 604 | SCLC | Metastatic | 1st line | Pembrolizumab | Placebo + VP-16 + CDDP/CBDCA | Hepatitis | 223 | 223 | [64] |
| Schmid P1 | 2020 | IMpassion 130 | Breast | Advanced | 1st line | Atezolizumab | Placebo + nab-PTX | Hepatitis, AST, ALT | 453 | 437 | [65] |
| Schmid P2 | 2020 | KEYNOTE 522 | Breast | Stage II–III | Neoadjuvant | Pembrolizumab | Placebo + CBDCA + PTX—> AC/EC | Hepatitis, AST, ALT | 781 | 389 | [66] |
| Shitara K | 2020 | KEYNOTE 062 | Gastric | Advanced | 1st line | Pembrolizumab | Placebo + 5-FU/Capecitabine + CDDP | Hepatitis | 250 | 244 | [67] |
| Socinski MA | 2018 | IMpower 150 | NSCLC | Metastatic | 1st line | Atezolizumab | CBDCA + PTX + Bevacizumab | Hepatitis, AST, ALT | 393 | 394 | [68] |
| Sugawara S | 2021 | TASUKI-52 | NSCLC | Advanced | 1st line | Nivolumab | Placebo + CBDCA + PTX + Bevacizumab | Hepatitis | 273 | 275 | [69] |
| West H | 2019 | IMpower 130 | NSCLC | Metastatic | 1st line | Atezolizumab | CBDCA + nabPTX | Hepatitis, AST, ALT | 473 | 232 | [70] |
*Data from two different articles were used for analysis. **Data from Goldman et al. were used for analysis. ***Data from Gandhi et al. were used for analysis
5-FU 5-fluorouracil; AC adriamycin + cyclophosphamide; ADR adriamycin; AST aspartate aminotransferase; ALT alanine aminotransferase; BSC best supportive care; CAPOX capecitabine + oxaliplatin; CBDCA carboplatin; CDDP cisplatin; CPA cyclophosphamide; CRT chemoradiotherapy; EC epirubicin + cyclophosphamide; FOLFOX 5-fluorouracil + oxaliplatin; GEJ gastroesophageal junction; GEM gemcitabine; HCC hepatocellular carcinoma; mCRPC metastatic castration-resistant prostate cancer; nabPTX nab-paclitaxel; NSCLC non-small cell lung cancer; PEM pemetrexed; PLD pegylated liposomal doxorubicin; PTX paclitaxel; SCLC small cell lung cancer; VP-16 etoposide