Table 2.
Overview of actionable targets and clinical studies on targeted therapies in established brain metastasis
| Target | Targeted Agent | Pretreatment with Radiotherapy |
Response Rate | Progression-free Survival (mo) | Overall Survival | Type of Trial | Reference or Clinicaltrials.Gov |
|---|---|---|---|---|---|---|---|
| HER2, EGFR | Lapatinib | Yes | 6% | 2.4 | 6.4 | Phase II | 81 |
| Lapatinib + Capecitabine |
No | 66% | 5.5 | ˃70% (1 y) |
Phase II | 83 | |
| Her2 | Neratinib | Yes | 8% | 1.9 | 8.7 | Phase II | 94 |
| Neratinib + Capecitabine |
Yes | 49% | NA | 63% (1 y) |
Phase II | 95(preliminary results) | |
| Tucatinib (ONT- 380) + (TDM1) | Yes | 33% | 6.5 | NA | Phase I | 97 | |
| PARP | Iniparib c | Yes | 27% | 2.14 | NA | Phase II | 102 |
| HER2 | Pertuzumab + High-dose Trastuzumab (intravenous) |
Yes | NA | NA | NA | Phase II | NCT02536339 |
| Pertuzumab + Trastuzumab (intrathecal) |
No | NA | NA | NA | Phase I | NCT02598427 | |
| Tucatinib (ONT- 380) + Trastuzumab |
Yes | NA | NA | NA | Phase I | NCT019221335 | |
| CDK4/6 | Abemaciclib | Yes | NA | NA | NA | Phase II | NCT02774681 |
| Palbociclib | No | NA | NA | NA | Phase II | NCT02308020 | |
| P13K/Akt | Everolimus | Yes | NA | NA | NA | Phase II |
NCT01305941 a NCT01783756 b |
| PARP | Veliparib | Yes (in association) |
NA | NA | NA | Phase II | NCT00649207 |
TDM1, trastuzumab emtansine; CDK4/6, cyclin-dependent kinase 4 and 6; Akt, protein kinase B; NA, not available.
aIn association with trastuzumab and vinorelbine. bIn association with lapatinib and capecitabine. cIn association with irinotecan.