Table 1.
Comparison of the results on the immune checkpoint and BRAF and MEK inhibitors in melanoma patients with brain metastases
| Study | Patient characteristics | ICR [%] (CR + PR) | ICC [%] (CR + PR + SD) | ECR [%] (CR + PR) | ECC [%] (CR + PR + SD) | IC DR (months) | EC DR (months) | Median PFS (months) | Median OS (months) |
|---|---|---|---|---|---|---|---|---|---|
| Combi-MB [40] (dabrafenib + trametinib) | Cohort A (V600E, asympt, no local therapy); 37% LDH > ULN; 66% ECOG = 0; 11% ≥ 4 MBM; n = 76 | 58 (4% CR) | 78 | 55 (4% CR) | 79 | 6.5 | 10.2 | 5.6 | 10.8 |
| Cohort B (V600E, asympt, local therapy); 19% LDH > ULN; 69% ECOG = 0; 0% ≥ 4 MBM; n = 16 | 56 (6% CR) | 88 | 44 (6% CR) | 69 | 7.3 | NE | 7.2 | 24.3 | |
| Cohort C (V600D/K/R, asympt, [no] local therapy); 38% LDH > ULN; 75% ECOG = 0; 6% ≥ 4 MBM; n = 16 | 44 (0% CR) | 75 | 75 (0% CR) | 94 | 8.3 | 4.9 | 4.2 | 10.1 | |
| Cohort D (V600D/E/K/R, sympt, [no] local therapy); 29% LDH > ULN; 53% ECOG = 0; 12% ≥ 4 MBM; n = 17 | 59 (6% CR) | 82 | 41 (0% CR) | 65 | 4.5 | 5.9 | 5.5 | 11.5 | |
| BREAK-MB [38] (dabrafenib) Cohort A: 55% LDH > ULN; 54% ECOG = 0; 9% ≥ 4 MBM Cohort B: 53% LDH > ULN; 61% ECOG = 0; 17% ≥ 4 MBM |
Cohort A (no local therapy) + V600E; n = 74 | 39.2 (3% CR) | 81.1 | ND | ND | 4.6 | ND | 3.7 | 7.6 |
| Cohort A (no local therapy) + V600 K; n = 15 | 6.7 (0% CR) | 33.3 | ND | ND | 2.9 | ND | 1.9 | 3.8 | |
| Cohort B (local therapy) + V600E; n = 65 | 30.8 (0% CR) | 89.2 | ND | ND | 6.5 | ND | 3.8 | 7.2 | |
| Cohort B (local therapy) + V600 K; n = 18 | 22.2 (0% CR) | 50.0 | ND | ND | 3.8 | ND | 3.7 | 5.0 | |
| McArthur et al. [39] (vemurafenib) | Cohort 1 (no local therapy; 57% LDH > ULN; 47% ECOG = 0); 14% ≥ 4 MBM; n = 90 | 18 (2% CR) | 61 | 33 (1% CR) | 80 | 4.6 | 7.7 | 3.7 (brain only) | 8.9 |
| Cohort 2 (local therapy; 52% LDH > ULN; 38% ECOG = 0); 18% ≥ 4 MBM; n = 56 | 18 (0% CR) | 59 | 23 (0% CR) | 78 | 6.6 | 11.1 | 4.0 (brain only) | 9.6 | |
| CheckMate 204 [53] (ipilimumab + nivolumab) | n = 75; no neurological symptoms; 12% previous treatment with BRAFi/MEKi; 41% LDH > ULN; 21% ≥ 3 MBM | 55 (21% CR) | 60 | 49.3 (7% CR) | 52 | NR; at 6 mo: 67% | NR | NR | NR |
| ABC [51] (nivolumab vs ipilimumab + nivolumab) | Cohort A: I + N (asympt, no local therapy); 42% LDH > ULN; 73% ECOG = 0; 46% ≥ 4 MBM; n = 26 | 42 (15% CR) | 50 | 48 (10% CR) | 67 | 4.8 (PFS) | 5.3 (PFS) | ND | NR |
| Cohort B: N (asympt, no local therapy); 58% LDH > ULN; 64% ECOG = 0; 20% ≥ 4 MBM; n = 25 | 20 (12% CR) | 24 | 30 (10% CR) | 40 | 2.7 (PFS) | 2.7 (PFS) | ND | NR | |
| Cohort C: N (sympt or local therapy or LM); 38% LDH > ULN; 50% ECOG = 0; 50% ≥ 4 MBM; n = 16 | 6 (0% CR) | 31 | 25 (8% CR) | 42 | 2.5 (PFS) | 2.7 (PFS) | ND | NR | |
| Margolin et al. [49] (ipilimumab 4 × 10 mg/kg Q3W); ≥ 1 MBM 0.5–3 cm or 2 > 0.3 cm | Cohort A (asympt, no SCS); 61% RTx; LDH: ND; 49% ECOG = 0; n = 51 | 16 (0% CR) | 24 | 14 (0% CR) | 27 | 1.5 | 2.6 | 1.4 | 7.2 (approx.) |
| Cohort B (sympt, SCS); 43% RTx; LDH: ND; 67% ECOG = 0; n = 21 | 5 (5% CR) | 10 | 5 (0% CR) | 5 | 1.2 | 1.3 | 1.2 | 3.9 (approx.) | |
| Goldberg et al. [50] (pembrolizumab 10 mg/kg Q2W) | n = 18 (asympt, 33% ECOG = 0, 39% LDH > ULN; 67% local therapy, median 2 MBM) | 22 (0% CR) | 27 | 22 (11% CR) | 44 | NR | NR | NR | NR |
asympt. asymptomatic, CR complete response, ECC extracranial control rate, EC DR duration of extracranial response rate, ECOG Eastern Cooperative Oncology Group ECR extracranial response rate, ICC intracranial control rate, IC DR duration of intracranial response rate, ICR intracranial response rate, LDH lactate dehydrogenase, LM leptomeningeal metastases, MBM melanoma brain metastases, n number patients, ND no data, NE not estimable, NR not reached, OS overall survival, PFS progression-free survival, PR partial response, QxW every x weeks, RTx previous radiotherapy to the brain (whole brain radiotherapy or stereotactic radiosurgery), SCS systemic corticosteroids, SD stable disease, sympt symptomatic, ULN upper limit of normal