eTable. Studies of the treatment of cerebral metastases.
| Studie | Treatment arm | Cohort under study | Number of patients | Follow-up | Number of cerebral target lesions | Intracranial response (patients/percentages) | ||
| (29) | Dabrafenib 150 mg BID + trametinib 2 mg/d | BRAFV600E mutation, asymptomatic cerebral metastases, without previous cerebral local therapy, ECOG status 0/1 | 76 | 8.5 months (median) | 1 2 3 4 5 |
41 (54%) 20 (26%) 7 (9%) 4 (5%) 4 (5%) |
CR PR SD PD Not evaluable |
3 (4%) 41 54%) 15 20%) 14 18%) 3 (4%) |
| BRAFV600E mutation, asymptomatic cerebral metastases, previous cerebral local therapy, ECOG status 0/1 | 16 | 20.0 months (median) | 1 2 3 4 5 |
7 (44%) 7(44%) 2 (13%) 0 0 |
CR PR SD PD Not evaluable |
1 (6%) 8 (50%) 4 (31%) 1 (6%) 1 (6%) |
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| BRAFV600D/K/R mutation, previous cerebral local therapy permitted, ECOG status 0/1 | 16 | 9.5 months (median) | 1 2 3 4 5 |
7 (44%) 6 (38%) 2 (13%) 0 1 (6%) |
CR PR SD PD Not evaluable |
0 7 (44%) 5 (31%) 4 (25%) 0 |
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| BRAFV600D/E/K/R mutation, asymptomatic cerebral metastases, previous cerebral local therapy permitted, ECOG status 0–2 | 17 | 11.0 months (median) | 1 2 3 4 5 |
7 (41%) 7 (41%) 1 (6%) 1 (6%) 1 (6%) |
CR PR SD PD Not evaluable |
1 (6%) 9 (53%) 4 (24%) 3 (18%) 0 |
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| (30) | Vemurafenib 960 mg BID | Therapy naive patients regarding cerebral metastases, previous systemic therapy permitted (excluding BRAF- or MEK- inhibitors) | 90 | 9.6 months (median) | 1 2–4 >4 |
40 (44%) 37 (41%) 13 (14%) |
CR PR SD PD Not evaluable |
2 (2%) 24 (27%) 36 (40%) 25 (28%) 3 (3%) |
| Previous treatment with stereotactic surgery, whole brain radiotherapy, or cerebral metastasectomy, measurable cerebral disease progression | 56 | 1 2–4 >4 |
11 (20%) 35 (63%) 10 (18%) |
CR PR SD PD Not evaluable |
0 13 (23%) 30 (54%) 11 (20%) 2 (4%) |
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| (31) | NIVO/IPI*1 | Asymptomatic cerebral metastases, no previous metastasectomy, stereotactic surgery or whole brain radiotherapy | 36 | 17 months (median) | 1 2–4 >4 |
11 (31%) 10 (29%) 14 (40%) |
CR PR SD PD Not evaluable |
6 (17%) 10 (29%) 4 (11%) 14 (40%) 1 (3%) |
| Nivolumab 3 mg/kg body weight, q14 | Asymptomatic cerebral metastases, no previous metastasectomy, stereotactic surgery or whole brain radiotherapy | 27 | 1 2–4 >4 |
6 (24%) 14 (56%) 5 (20%) |
CR PR SD PD Not evaluable |
3 (12%) 2 (8%) 0 19 (76%) 1 (4%) |
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| Symptomatic cerebral metastasis or progressive or new cerebral metastases after local pre-treatment or leptomeningeal disease or the combination of these | 16 | 1 2–4 >4 |
1 (6%) 7 (44%) 8 (50%) |
CR PR SD PD Not evaluable |
0 1 (6%) 2 (13%) 13 (81%) 0 |
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| (32) | NIVO/IPI*1 | Asymptomatic cerebral metastases, no previous metastasectomy, stereotactic surgery or whole brain radiotherapy | 94*2 | 14 months (median) | 1 2 ≥ 3 |
49 23 22 |
CR PR SD (≥ 6 months) PD Not evaluable |
24 (26%) 28 (30%) 2 (2%) 31 (33%) 9 (10%) |
*1 Nivolumab 1 mg/kg body weight+ ipilimumab 3 mg/kg body weight q21 for 4 cycles, followed by nivolumab 3 mg/kg body weight; q14: every two weeks;
*2 a patient without measurable cerebral lesions
BID, twice per day; CR, complete remission; PR, partial remission; PD, progressive disease; SD, stable disease