Table 3.
Neurologic adverse effects reported on clinical trials involving previously untreated brain metastases
| Study Name or ClinicalTrials.gov identifier | Phase | Disease | Intervention | Neurologic symptoms | Steroid | Neurologic AEs (any grade) | Neurologic SAEs (grades 3–4) | Headache | Dizziness | Confusion | Seizure | Ataxia | Edema | Hemorrhage | RN | Citation |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Immunotherapy | ||||||||||||||||
| CA184–042 NCT00623766 | 2 | Melanoma | Ipilimumab | Asymptomatic | Prohibited | N.R. | N.R. | 18 (35%) | 11 (22%) | 9 (18%) | N.R. | N.R. | 3 (6%) | N.R. | N.R. | Margolin et al. |
| Symptomatic | Allowed | N.R. | N.R. | 6 (29%) | 2 (10%) | 3 (14%) | N.R. | N.R. | N.R. | N.R. | N.R. | |||||
| NIBIT-M1 NCT01654692 | 2 | Melanoma | Ipilimumab/Fotemustine | Asymptomatic | Prohibited | 5 (25%) | 2 (10%) | N.R. | N.R. | N.R. | N.R. | N.R. | N.R. | N.R. | N.R. | Di Giacomo et al. |
| NCT02085070 | 2 | Melanoma and NSCLC | Pembrolizumab | Asymptomatic | Prohibited | N.R. | 1 (4%) | 4 (17%) | 2 (9%) | 3 (13%) | 3 (13%) | 5 (22%) | 4 (17%) | 1 (4%) | 7 (30.4%) | Goldberg et al. and Kluger et al. |
| CheckMate-204 NCT02320058 | 2 | Melanoma | Ipilimumab/Nivolumab | Asymptomatic | Prohibited | 34 (36%) | 7 (7%) | 21 (22%) | 1 (1%) | N.R. | 2 (2%) | N.R. | 2 (2%) | 2 (2%) | N.R. | Tawbi et al. |
| ABC NCT02374242 | 2 | Melanoma | Ipilimumab/Nivolumab | Asymptomatic | Prohibited | 11 (31%) | 2 (6%) | 4 (11%) | 1 (3%) | N.R. | 1 (3%) | N.R. | N.R. | N.R. | 0 (0%) | Long et al. |
| Nivolumab | Asymptomatic | Prohibited | 6 (24%) | 0 (0%) | 5 (20%) | 1 (4%) | N.R. | 0 (0%) | N.R. | N.R. | N.R. | 0 (0%) | ||||
| Nivolumab (after local therapy failure or symptoms) | Symptomatic | Prohibited | 2 (13%) | 2 (13%) | 1 (6%) | 0 (0%) | N.R. | 0 (0%) | N.R. | N.R. | N.R. | 1 (6%) | ||||
| Immunotherapy with radiation | ||||||||||||||||
| NCT01703507 | 1 | Melanoma | Ipilimumab and WBRT | N.R. | N.R. | N.R. | 0 (0%) | 2 (40%) | 1 (20%) | N.R. | 0 (0%) | N.R. | 0 (0%) | 0 (0%) | 0 (0%) | Williams et al. |
| Ipilimumab and SRS | N.R. | N.R. | N.R. | 0 (0%) | 5 (45%) | 0 (0%) | N.R. | 1 (9%) | N.R. | 0 (0%) | 4 (36%) | 0 (0%) | ||||
AE, adverse event; N.R., not reported; NSCLC, non-small cell lung cancer; RN, radiation necrosis; SRS, stereotactic radiosurgery; WBRT, whole brain radiotherapy.