Summary of clinical information on the eight studied EGFR inhibitors
| Compound | Clinical Status | Dose in Patients | Brain Penetration (% of CSF to Plasma Levels) in Patient | Brain Penetration (% of Brain-to-Plasma Ratio) in Preclinical Model | Response Rate in Patients with Primary Brain Tumor | Response Rate in Patients with Brain Metastases | References |
|---|---|---|---|---|---|---|---|
| mg/day | % | % | |||||
| AEE788 | Terminated | 50–800 | ND | ND | GBM, stable disease (17) | ND | Reardon et al. (2012) |
| Afatinib | Giotrif | 50 | 0.7 | ND | GBM, stable disease (14) | 35 | Wind et al. (2014), Hoffknecht et al. (2015), Reardon et al. (2015) |
| AZD3759 | Phase I (fast review) | 100–1000 | 111 | 282 | ND | 83 | Zeng et al. (2015), Ahn et al. (2017), Xiong et al. (2017) |
| Dacomitinib | Phase 2–3 | 45/60 | NA | NA | ND | 6.3a | |
| Erlotinib | Tarceva | 150 | 2.77–5.1 | 13.7 | GBM, PFS6 (3); first-relapse GBM, OR (6.3) | 82.4 (EGFR mutation) | Raizer et al. (2010), Togashi et al. (2010), Yung et al. (2010), Porta et al. (2011), de Vries et al. (2012) |
| Gefitinib | Iressa | 750–1000 | 1.07–3.58 | 27 | Astrocytoma, overall disease-control rate (17.9); GBM, overall disease-control rate (12.5) | 27 | Ceresoli et al. (2004), Franceschi et al. (2007), Chen et al. (2013) |
| Osimertinib | Tagrisso | 80 | NA | 180 | ND | 54 (T790M+) | Ballard et al. (2016), Goss et al. (2018) |
| Vandetanib | Caprelsa | 300 | 1.2–2.4 | 21 | GBM, objective response rate (12.5) | ND | Kreisl et al. (2012) |
GBM, glioblastoma; NA, not available; ND, not determined; OR, objective rate; PFS6, progression-free survival at 6 months.
↵a From clinicaltrials.gov (identifier: NCT01858389).