Table 1.
Summary of selected studies of targeted therapies in brain metastases.
| Targeted therapy | Primary malignancy | Study design | Number of patients with brain metastases | Outcomes |
|---|---|---|---|---|
| ALK DIRECTED THERAPY | ||||
| Crizotinib (29) | NSCLC | Subgroup analysis of a phase 3 trial | • 79 patients with stable BM • 39 treated with crizotinib • 40 treated with standard chemotherapy |
12 week DCR 85% in the crizotinib group compared to 45% in the chemotherapy group |
| Ceritinib (32) | NSCLC | Subgroup analysis of a phase 2 trial | • 100 patients had asymptomatic BM • 20 had measurable BM |
IC-RR: 45% |
| Alectinib (35) | NSCLC | Pooled analysis of two phase 2 trials | 136 patients with BM who had progressed on crizotinib | IC-RR: 64% |
| Brigatinib (38) | NSCLC | Subgroup analysis of phase 2 trial | 40 patients in the brigatinib group and 41 patients in the crizotinib had brain metastases | IC-RR: 78% in the brigatinib group compared to 29% in the crizotinib group |
| BRAF-MEK DIRECTED THERAPY | ||||
| Vemurafenib (52) | Melanoma | Phase 2 trial | • 90 patients with previously untreated BM | IC-RR: 18% |
| Dabrafenib (54) | Melanoma | Phase 2 trial | • 172 patients with BRAF mutant melanoma and BM | IC-RR of 40% in treatment naïve and 30% in previously treated patients |
| Dabrafenib and trametinib (57) | Melanoma | Multicenter, multicohort phase 2 trial | • Cohort A: 76 patients with BRAFV600E mutation, good PS, asymptomatic and newly diagnosed BM • Cohort B: 16 patients with BRAFV600E, good PS, asymptomatic but progressive BM • Cohort C: 16 patients, asymptomatic, good PS, BRAFV600D/K/R • Cohort D: 17 patients, symptomatic, BRAFV600E/D/K/R |
IC-RR in Cohort A: 58% IC-RR in Cohort B: 56% IC-RR in Cohort C: 44% IC-RR in Cohort D: 59% |
| EGFR DIRECTED THERAPY | ||||
| Erlotinib (67) | NSCLC | Phase 2 trial | • 48 patients with progressive BM | IC-PFS: 10.1 months |
| Erlotinib (68) | NSCLC | Phase 2 trial | • 40 patients with progressive BM, concurrent with radiation | IC-RR: 60% |
| Erlotinib (66) | NSCLC | Phase 3 trial | • 41 patients treated with WBRT/SRS plus erlotinib | MST: 6.1 months 6 month IC-DCR: 10% |
| Osimertinib (75) | NSCLC | Phase 3 trial | • 61 patients treated with osimertinib 67 patients treated with standard EGFR-TKI |
PFS at 6 months: 87% vs. 71%. PFS at 18 months: 58% vs. 40% |
| HER2 DIRECTED THERAPY | ||||
| Lapatinib plus capecitabine (95) | Breast cancer | Phase 2 trial | • 45 patients with BM | IC-RR: 66% |
| Neratinib plus capecitabine (98) | Breast cancer | Phase 2 trial | • 39 patients with BM | 12 month OS: 63% |
| IMMUNOTHERAPY | ||||
| Ipilimumab plus nivolumab (104) | Melanoma | Phase 2 trial | • 94 patients with BM | IC benefit: 57% |
| Pembrolizumab (105, 106) | Melanoma NSCLC | Phase 2 trial | • 23 patients with BM 18 patients with BM |
IC-RR: 26% IC-RR: 33% |
NSCLC, Non-small cell lung cancer; BM, brain metastases; DCR, disease control rate; IC-RR, Intracranial response rate; MST, median survival time; OS, overall survival; PFS, progression free survival; IC benefit, 6 month stable disease, complete or partial response.