Table 1.
Baseline characteristics of included publications.
| Author | Year | Patient number | Region | Male (%) | Median age | ECOG PS 0-1/2 | Cancer type | ICI treatment | Treatment line | ICI monotherapy or association | PPI | No PPI | PPI treatment | PPI use window |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Afzal (17) | 2019 | 120 | America | NA | 65 | NA | Melanoma | Pembrolizumab, nivolumab, ipilimumab | NA | Monotherapy or association | 29 | 91 | Omeprazole (majority) | At the start of ICI |
| Araujo (18) | 2021 | 216 | America | NA | 59 | 199/17 | Multiple | Anti PD1, anti PD-L1 | NA | NA | 57 | NA | NA | 60 days prior ICIs initiation |
| Baeck (19) | 2022 | 1,646 | Asia | 1,323 (80) | 66 | NA | NSCLC | Pembrolizumab, nivolumab, atezolizumab | Second or beyond | NA | 823 | 823 | NA | Within 30 days prior ICIs initiation |
| Buti (20) | 2021 | 217 | Europe | 148 (68,2) | 69 | 189/28 | Multiple | Anti-PD-1, anti PD-L1, anti-CTLA-4 | First, second, or beyond | Monotherapy | 104 | 113 | NA | NA |
| Castro Balado (21) | 2021 | 49 | Europe | 37 (75,5) | 66 | NA | NSCLC | Pembrolizumab | First | Monotherapy | 26 | 23 | NA | NA |
| Chalabi (10) | 2020 | 757 | America/Europe | 471 (62,2) | NA | 755/NA | NSCLC | Atezolizumab | Second or beyond | Monotherapy | 234 | 523 | Omeprazole (majority) | Within 1 month before or after ICIs initiation |
| Conde-Estevez (22) | 2021 | 70 | Europe | 53 (75,7) | 66 | 62/8 | NSCLC | Atezolizumab, pembrolizumab, nivolumab | Second or beyond | Monotherapy | 59 | 11 | NA | NA |
| Cortellini (23) | 2020 | 1,012 | Europe | 647 (63,9) | 69 | 870/142 | Multiple | Nivolumab, pembrolizumab, atezolizumab | First, second, or beyond | Monotherapy | 491 | 521 | NA | NA |
| Cortellini (24) | 2021 | 950 | Europe | 625 (65,8) | 70 | 785/165 | NSCLC | Pembrolizumab | First | Monotherapy | 474 | 476 | NA | NA |
| Failing (25) | 2016 | 80 | America | NA | 58 | NA | Melanoma | Ipilimumab | First | Monotherapy | 17 | 63 | Omeprazole (majority), pantoprazole, esomeprazole, lansoprazole | At the start of ICI |
| Fukuokaya (26) | 2022 | 227 | Asia | 165 (72,7) | 70 | NA | Urothelial carcinoma | Pembrolizumab | Second or beyond | Monotherapy | 86 | 141 | Esomeprazole, lansoprazole, omeprazole, rabeprazole, vonoprazan | Within 1 month before or after ICIs initiation |
| Gaucher (27) | 2021 | 372 | Europe | 244 (65,6) | 64 | 295/77 | Multiple | Ipilimumab, nivolumab, pembrolizumab | First, second, or beyond | Monotherapy or association | 149 | 223 | NA | At the ICI initiation or in the following 60 days |
| Giordan (28) | 2021 | 212 | Europe | 143 (68) | 64 | 161/50 | Multiple | Nivolumab, pembrolizumab, ipilimumab | First, second, or beyond | Monotherapy or association | 74 | 138 | Omeprazole, pantoprazole, esomeprazole, lansoprazole, rabeprazole |
Within 30 days prior ICIs initiation |
| Hakozaki (29) | 2018 | 90 | Asia | 57 (63,3) | 67 | 64/26 | NSCLC | Nivolumab | Second or beyond | Monotherapy | 47 | 43 | NA | Within 30 days prior ICIs initiation |
| Homicsko (30) | 2022 | 1,505 | Majority America/Europe | 951 (63,2) | NA | 1,498/7 | Melanoma | Nivolumab, ipilimumab | First | Monotherapy or association | 291 | 1,214 | Omeprazole, pantoprazole, esomeprazole, lansoprazole, rabeprazole, dexlansoprazole |
Within 30 days prior ICIs initiation |
| Hopkins (31) | 2020 | 1,360 | America/Europe | NA | 68 | 1,336/24 | Urothelial carcinoma | Atezolizumab | First, second | Monotherapy | 471 | 889 | Omeprazole, pantoprazole, esomeprazole, lansoprazole, rabeprazole, dexlansoprazole |
Within 30 days prior or after ICIs initiation |
| Hopkins (32) | 2021 | 1,202 | Worldwide | 720 (59,9) | 63 | 1,202/0 | NSCLC | Atezolizumab | First | Association | 441 | 761 | Omeprazole, pantoprazole | Within 30 days prior or after ICIs initiation |
| Hossain (33) | 2020 | 63 | Oceania | NA | NA | NA | NSCLC | NA | NA | NA | 34 | 29 | NA | 30 days after ICIs initiation |
| Husain (34) | 2021 | 1,091 | America | 647 (59,3) | 62 | 813/184 | Multiple | Anti PD1, anti PD-L1, anti CTLA-4, other | First, second, or beyond | NA | 415 | 676 | NA | At the same time of ICI |
| Iglesias-Santamaria (35) | 2019 | 102 | Europe | 84 (82,2) | 66 | 91/4 | Multiple | Ipilimumab, nivolumab, pembrolizumab, atezolizumab | First, second, or beyond | NA | 78 | 23 | NA | NA |
| Jun (36) | 2021 | 314 | America/Europe/Asia | 248 (79) | 66 | NA | Hepatocellular carcinoma | Anti PD-1, anti CTLA-4 | First, second, or beyond | Monotherapy or association | 85 | 229 | Omeprazole, pantoprazole esomeprazole, lansoprazole Rabeprazole dexlansoprazole |
Within 30 days prior ICI initiation |
| Kostine (37) | 2021 | 634 | Europe | 443 (70) | 65 | 528/98 | Multiple | Anti-CTLA-4, anti-PD1, anti-PD-L1 | First or beyond | NA | 239 | 396 | Omeprazole, pantoprazole, lansoprazole, rabeprazole | Within 30 days before or after ICIs initiation |
| Kulkarni (38) | 2019 | 203 | Europe | NA | NA | NA | Multiple | Anti-PD-1, anti-PD-L1 | NA | NA | 74 | 129 | NA | Within 1 month before ICIs initiation |
| Kunimitsu (39) | 2022 | 79 | Asia | 59 (74,7) | 72 | 56/23 | Urothelial carcinoma | Pembrolizumab | First, second, or beyond | Monotherapy | 45 | 34 | Lansoprazole, esomeprazole, rabeprazole, vonoprazan | within 60 days prior and/or 30 days after treatment initiation |
| Miura (40) | 2021 | 300 | Asia | 226 (75,3) | 65 | 246/54 | NSCLC | Nivolumab, pembrolizumab | First, second, or beyond | Monotherapy | 163 | 137 | NA | NA |
| Mollica (41) | 2021 | 219 | America/Europe | 155 (71) | 61 | NA | Renal cell carcinoma | Nivolumab, ipilimumab | First, second, or beyond | Monotherapy or association | 113 | 106 | NA | 30 days before ICIs initiation |
| Nguyen (42) | 2019 | 95 | Asia | 62 (65,3) | 68 | NA | Multiple | Nivolumab | NA | Monotherapy | 40 | 55 | NA | 2 weeks during the ICI administration |
| Okuyama (43) | 2022 | 155 | Asia | 109 (70,3) | 72 | 121/34 | Urothelial carcinoma | Pembrolizumab, nivolumab, atezolizumab, and durvalumab | Second or beyond | NA | 99 | 56 | NA | Within 30 days before or during the ICI therapy |
| Peng (44) | 2022 | 233 | America | 130 (55,8) | 64 | 186/47 | Multiple | Nivolumab, pembrolizumab, and ipilimumab | First, second, or beyond | Monotherapy or association | 89 | 144 | NA | Within 30 days before or after ICIs initiation |
| Perez-Ruiz (45) | 2020 | 253 | Europe | 176 (70) | 61 | 216/31 | Multiple | Anti-CTLA-4, anti-PD-1 | First, second, or beyond | NA | 135 | 118 | NA | Within 60 days prior to 30 days after |
| Rassy (46) | 2022 | 707 | Europe | 546 (72,2) | 64 | 568/103 | Renal cell carcinoma | Nivolumab | Second or beyond | Monotherapy | 196 | 511 | NA | At the same time of ICI |
| Routy (47) | 2017 | 249 | Europe | 177 (71,1) | 63 | NA | Multiple | Anti-PD-1, anti-PD-L1, anti-CTLA-4 | First, second, or beyond | Monotherapy or association | 187 | 62 | NA | Within 60 days prior to 30 days after |
| Ruiz-Banobre (48) | 2021 | 119 | Europe | 96 (81) | 69 | 99/20 | Urothelial carcinoma | Atezolizumab, pembrolizumab, nivolumab, durvalumab | First, second, or beyond | Monotherapy | 54 | 65 | NA | Within 30 days prior ICI initiation |
| Spakowicz (49) | 2020 | 689 | America | 402 (58.3) | 62 | 457/139 | Multiple | Atezolizumab, pembrolizumab, nivolumab, durvalumab and tremelimumab | NA | NA | 255 | 434 | NA | Within 30 days prior ICI initiation |
| Stein (50) | 2021 | 232 | Europe | NA | NA | NA | Melanoma | Nivolumab, pembrolizumab | First or beyond | NA | 86 | 146 | NA | At the same time of ICI |
| Stokes (51) | 2021 | 3,634 | America | 3,525 (97) | 69 | NA | NSCLC | Nivolumab, pembrolizumab, durvalumab, and atezolizumab | NA | NA | 2,159 | 1,475 | Omeprazole (majority) | Within 90 days ICIs initiation |
| Svaton (52) | 2020 | 224 | Europe | 133 (59,3) | 67 | 220/4 | NSCLC | Nivolumab | First, second, or beyond | NA | 64 | 160 | Omeprazole, pantoprazole lansoprazole | Within 30 days before or after ICIs initiation |
| Takada (53) | 2022 | 95 | Asia | 78 (82,1) | 69 | 89/6 | NSCLC | Nivolumab, pembrolizumab, and atezolizumab | NA | Monotherapy or chemotherapy combination | 37 | 58 | Esomeprazole, lansoprazole Rabeprazole, omeprazole, vonoprazan |
the same time of ICI |
| Tomita (54) | 2022 | 118 | Asia | 99 (83,8) | 68 | 52/20 | NSCLC | Nivolumab, pembrolizumab, and atezolizumab | First, second, or beyond | Monotherapy or chemotherapy combination | 72 | 46 | Esomeprazole, lansoprazole Rabeprazole, omeprazole, vonoprazan |
Within 30 days before or after ICIs initiation |
| Tomizaki (55) | 2022 | 40 | Asia | 30 (75) | 72 | NA | Urothelial carcinoma | Pembrolizumab | Second or beyond | Monotherapy | 15 | 25 | NA | Within 60 days before or 30 days after ICIs initiation |
| Zaho (13) | 2019 | 109 | Asia | 89 (81,7) | 62 | 107/2 | NSCLC | Pembrolizumab, nivolumab, and camrelizumab | First, second, or beyond | Monotherapy or chemotherapy combination | 40 | 69 | NA | Within 1 month before or after ICIs initiation |
PPI, proton pump inhibitor; ICI, immune checkpoint inhibitor; NA, not available; ECOG PS, Eastern cooperative group performance status; NSCLC, non-small cell lung cancer; ICI, immune checkpoint inhibitor; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4.