Table 2.
Distribution of therapeutic indication ICI therapies involved in the neurological complications collected in the European database EudraVigilance until February 7, 2020.
| Therapeutic indications | ICSRs | Atezolizumab | Avelumab | Cemiplimab | Durvalumab | Ipilimumab | Nivolumab | Pembrolizumab | Ipilimumab/nivolumab | Other ICI combinations |
|---|---|---|---|---|---|---|---|---|---|---|
| N = 4,875 | N = 272 | N = 33 | N = 12 | N = 122 | N = 582 | N = 1,849 | N = 1,514 | N = 457 | N = 34 | |
| (100%) | (5.58%) | (0.68%) | (0.25%) | (2.5%) | (11.94%) | (37.93%) | (31.06%) | (9.37%) | (0.7%) | |
| Lung cancer | 1,719 | 163 | 1 | – | 83 | 2 | 781 | 670 | 17 | 2 |
| (35.26%) | (59.92%) | (3.03%) | (68.03%) | (0.34%) | (42.24%) | (44.25%) | (3.72%) | (5.88%) | ||
| Melanoma | 1,293 | 4 | – | – | – | 396 | 259 | 328 | 280 | 26 |
| (26.52%) | (1.47%) | (68.16%) | (14.01%) | (21.66%) | (61.27%) | (76.47%) | ||||
| Genitourinary tract neoplasm | 577 | 47 | 5 | – | 1 | 8 | 290 | 116 | 109 | 1 |
| (11.83%) | (17.28%) | (15.15%) | (0.82%) | (1.37%) | (15.7%) | (7.66%) | (23.85%) | (2.94%) | ||
| Unknown indication | 505 | 24 | 5 | 3 | 14 | 112 | 146 | 170 | 29 | 2 |
| (10.35%) | (8.82%) | (15.15%) | (25%) | (11.47%) | (19.27%) | (7.9%) | (11.23%) | (6.34%) | (5.88%) | |
| Gastrointestinal tract cancer | 150 | 4 | – | – | 1 | – | 117 | 27 | 1 | – |
| (3.07%) | (1.47%) | (0.82%) | (6.33%) | (1.8%) | (0.22%) | |||||
| Head and neck cancer | 105 | 1 | 2 | – | 1 | – | 75 | 25 | 1 | – |
| (2.15%) | (0.37%) | (6.06%) | (0.82%) | (4.06%) | (1.65%) | (0.22%) | ||||
| Skin Cancer | 67 | – | 15 | 7 | – | 2 | 24 | 16 | 2 | 1 |
| (1.37%) | (45.45%) | (58.33%) | (0.34%) | (1.3%) | (1.06%) | (0.44%) | (2.94%) | |||
| Lymphoma | 67 | – | – | – | 1 | 52 | 13 | 1 | 0 | – |
| (1.37%) | (0.82%) | (8.95%) | (0.7%) | (0.07%) | ||||||
| Unspecified cancer | 56 | 3 | – | 1 | – | 1 | 30 | 18 | 3 | – |
| (1.15%) | (1.1%) | (8.33%) | (0.17%) | (1.62%) | (1.2%) | (0.66%) | ||||
| Breast cancer | 49 | 20 | 1 | – | 2 | – | 5 | 21 | – | – |
| (1%) | (7.35%) | (3.03%) | (1.64%) | (0.27%) | (1.4%) | |||||
| Female reproductive neoplasm | 41 | 3 | 2 | – | – | – | 8 | 27 | 1 | – |
| (0.84%) | (1.1%) | (6.06%) | (0.43%) | (1.8%) | (0.22%) | |||||
| Nervous system cancer | 39 | – | – | 1 | – | 1 | 25 | 7 | 5 | – |
| (0.8%) | (8.33%) | (0.17%) | (1.35%) | (0.46%) | (1.1%) | |||||
| Hepatic and bile duct cancer | 36 | – | – | – | 1 | 3 | 24 | 7 | 1 | – |
| (0.74%) | (0.82%) | (0.52%) | (1.31%) | (0.46%) | (0.22%) | |||||
| Respiratory tract cancer (excl. lung cancer) | 36 | 1 | – | – | 1 | – | 22 | 11 | 1 | – |
| (0.74%) | (0.37%) | (0.82%) | (1.21%) | (0.73%) | (0.22%) | |||||
| Mesothelioma | 33 | – | – | – | – | – | 10 | 20 | 3 | – |
| (0.68%) | (0.54%) | (1.32%) | (0.66%) | |||||||
| Pancreatic cancer | 31 | – | – | – | 16 | – | 2 | 13 | – | – |
| (0.63%) | (13.11%) | (0.11%) | (0.86%) | |||||||
| Neuroendocrine cancer | 29 | 1 | 1 | – | – | – | 5 | 18 | 2 | 2 |
| (0.6%) | (0.37%) | (3.03%) | (0.27%) | (1.2%) | (0.44%) | (5.88%) | ||||
| Metastases | 16 | – | – | – | – | 3 | 4 | 9 | – | – |
| (0.33%) | (0.52%) | (0.22%) | (0.6%) | |||||||
| Leukemia | 9 | 1 | 1 | – | – | 2 | 1 | 3 | 1 | – |
| (0.18%) | (0.37%) | (3.03%) | (0.34%) | (0.05%) | (0.21%) | (0.22%) | ||||
| Other indication a | 5 | – | – | – | – | – | 2 | 3 | – | – |
| (0.1%) | (0.1%) | (0.21%) | ||||||||
| Sarcoma | 5 | – | – | – | 1 | – | 1 | 2 | 1 | – |
| (0.1%) | (0.82%) | (0.05%) | (0.13%) | (0.22%) | ||||||
| More of an indication b | 3 | – | – | – | – | – | 3 | – | – | – |
| (0.06%) | (0.16%) | |||||||||
| Bone cancer | 3 | – | – | – | – | – | 1 | 2 | – | – |
| (0.06%) | (0.05%) | (0.13%) | ||||||||
| Mediastinum neoplasm | 1 | – | – | – | – | – | 1 | – | – | – |
| (0.02%) | (0.05%) |
a
“Other indication” includes multiple sclerosis, osteoporosis, progressive multifocal leukoencephalopathy, white blood cell count decreased, and mismatch repair cancer syndrome.
b
“More of an indication” includes “Brain neoplasm, malignant melanoma, non-Hodgkin’s lymphoma”, “endometrial cancer, metastases to lung, ovarian cancer”, and “Malignant melanoma, papillary thyroid cancer”.