Table 3.
Summary of incidence of immune-related diarrhea and colitis
| ICPI | Target | Author | Year | Plus other drugs | n | Cancer type | Any grade diarrhea/colitis, n (%) | Grade 3-5 diarrhea/colitis, n (%) |
| Nivolumab | PD-1 | Topalian et al[41] | 2012 | None | 296 | Solid cancer | 33 (11)/ND | 3 (1)/ND |
| Weber et al[42] | 2013 | None ipilimumab-naive | 34 | Melanoma | 13 (38.2)/0 (0) | Not observed1 | ||
| Ipilimumab-refractory | 56 | 11 (19.6)/0 (0) | ||||||
| Weber et al[43] | 2015 | None | 268 | Melanoma2 | 30 (11.2)/ND | 1 (0.4)/ND | ||
| Larkin et al[44] | 2015 | None | 315 | Melanoma | 60 (19.2)/4 (1.3) | 7 (2.2)/2 (0.6) | ||
| Ferris et al[45] | 2016 | None | 236 | SCCHN | 16 (6.8)/0 (0) | 0 (0)/0 (0) | ||
| Kang et al[46] | 2017 | None | 330 | GC/GEJC | 23 (7)/2 (1) | 2 (1)/1 (< 1) | ||
| Pembrolizumab | PD-1 | Hamid et al[47] | 2013 | None | 135 | Melanoma | 27 (20) | 1(1) |
| Garon et al[48] | 2015 | None | 495 | NSCLC | 40 (8.1)/ND | 3 (0.6)/ND | ||
| Ribas et al[49] | 2015 | None | 361 | Melanoma2 | 32 (8.9)/5 (1.4) | 2 (0.6)/2 (0.6) | ||
| Herbst et al[50] | 2016 | None | 690 | NSCLC | 46 (6.7)/6 (0.9) | 2 (0.3)/4 (0.6) | ||
| Ribas et al[51] | 2016 | None | 655 | Melanoma | 115 (18)/11(2) | 6 (1)/7 (1.1) | ||
| Mok et al[52] | 2019 | None | 636 | NSCLC | 34 (5)/7 (1) | 5 (< 1)/4 (< 1) | ||
| Ipilimumab | CTLA-4 | Weber et al[53] | 2008 | None | 88 | Melanoma | ND | 5 (5.6)/4 (4.5) |
| Weber et al[54] | 2009 | None | 57 | Melanoma | 20 (35)/ND | 10 (18)/ND | ||
| budesonide | 58 | 19 (33)/ND | 8 (14)/ND | |||||
| Wolchok et al[55] | 2010 | None | 214 | Melanoma | 58 (27)/ND | 11(5.1)/ND | ||
| Hodi et al[56] | 2010 | None | 131 | Melanoma | 43 (32.8)/10 (7.6) | 7 (5.3)/7 (5.3) | ||
| gp100 | 380 | 146 (38.4)/20 (5.3)3 | 17 (4.5)/12(3.2)3 | |||||
| Robert et al[57] | 2011 | Dacarbazine | 247 | Melanoma | 81 (32.8)/11 (4.5) | 10 (4.0)/5 (2.0) | ||
| Margolin et al[58] | 2012 | None | 72 | Melanoma | 30 (42)/ND | 6 (8.3)/ND | ||
| Kwon et al[59] | 2014 | None | 399 | Prostate cancer | 199 (51)/27 (7) | 64 (16)/18 (5) | ||
| Larkin et al[44] | 2015 | None | 311 | Melanoma | 103 (33.1)/36 (11.6) | 19 (6.1)/27 (8.7) | ||
| Eggermont et al[35] | 2016 | None | 471 | Melanoma | 194 (41.2)/73 (15.5) | 46 (9.8)/39 (8.2) | ||
| Ipilimumab plus nivolumab | CTLA4 and PD1 | Wolchok et al[60] | 2013 | None | 53 | Melanoma | 18 (34.0)/5 (9) | 3 (6)/2 (4) |
| Larkin et al[44] | 2015 | None | 315 | Melanoma | 138 (44.1)/37 (11.8) | 29 (9.3)/24 (7.7) | ||
| Schadendorf et al[61] | 2017 | None | 407 | Melanoma | 30 (7.4)/40 (9.8) | 25 (6.1)/32 (7.9) | ||
| Wolchok et al[62] | 2017 | None | 313 | Melanoma | 142 (45)/40 (13) | 29 (9)/26 (8) | ||
| Hellmann et al[63] | 2017 | None | 77 | NSCLC | 16 (21)/4 (5.2) | 1 (1.3)/3 (3.9) | ||
| Motzer et al[64] | 2018 | None | 547 | Renal cell carcinoma | 145 (27)/ND | 21 (4)/ND | ||
| Durvalumab | PD-L1 | Antonia et al[65] | 2017 | None | 473 | NSCLC | 87 (18.3)/ND | 3 (0.6)/ND |
| Motzer et al[66] | 2018 | None | 475 | NSCLC | 88 (18.5)/ND | 3 (0.6)/ND | ||
| Loibl et al[67] | 2019 | None | 92 | Breast cancer | 26 (28.3)/ND | 3 (3.3)/ND | ||
| Atezolizumab | PD-L1 | Herbst et al[68] | 2014 | None | 277 | Solid tumors or hematological malignancies | 29 (10.5)/ND | 0 (0)/ND |
| Rosenberg et al[69] | 2016 | None | 311 | Urothelial carcinoma | 24 (8)/3 (1) | 1 (0.3)/2 (1) | ||
| Fehrenbacher et al[70] | 2016 | None | 142 | NSCLC | ND | ND/2 (1) | ||
| Socinski et al[71] | 2018 | ABCP | 393 | NSCLC | 70 (17.8) | 11 (2.8) | ||
| Avelumab | PD-L1 | Chung et al[72] | 2019 | None | 150 | GC/GEJC | ND/2 (1.3) | ND/1 (0.7)4 |
| Barlesi et al[73] | 2019 | None | 396 | NSCLC | 24 (6)/ND | 0 (0)/ND |
1
Dose-limiting colitis was not observed in this trial;
2
Progressed after ipilimumab;
3
Immune-related event;
4
No atezolizumab-related grade 4 but adverse events were reported, but only one patient showed Grade 5 cardiac failure. SCCHN: Squamous cell carcinoma of the head and neck; NSCLC: Non-small-cell lung cancer; ABCP: Atezolizumab plus bevacizumab plus carboplatin plus paclitaxel; GC/GEJC: Gastric/gastroesophageal cancer; ND: Not described.