Table II.
Brain and Transporter Related Features of Molecularly Targeted Therapy for Lung Cancer
| Compound | Molecular target | Dose in patients (mg/day) | Brain penetration (% of CSF to plasma levels) in patient* | Brain penetration (% of brain to plasma ratio) in pre-clinical model* | Response rate in BM patients (%) | Transporter effect | Reference |
|---|---|---|---|---|---|---|---|
| Gefitinib | EGFR-TKI | 750–1000 | 1.07–3.58 | 27 | 27% | P-gp substrate | (109,192) |
| Erlotinib | EGFR-TKI | 150 | 2.77–5.1 | 13.7 | 82.4% (EGFR mutation) | P-gp and Bcrp substrate | (93,108,193) |
| Afatinib | EGFR-TKI | 50 | 0.7 | ND | 35% | P-gp substrate | (114,194) |
| Osimertinib | EGFR-TKI | 80 | NA | 180 | ND | P-gp and Bcrp substrate | (115) |
| AZD3759 | EGFR-TKI | 100–1000 | 1 1 1 | 282 | 83% | ND | (117) |
| Crizotinib | ALK-TKI | 500 | 0.26 | 23 | 18–33% | P-gp substrate but not Bcrp | (100) |
| Alectinib | ALK-TKI | 200 | 0.3 | 63–94 | 52% | Not a P-gp substrate | (127–129) |
| Ceritinib | ALK-TKI | 400 | ND | 15 | 34.5–58.8% | P-gp and Bcrp substrate | (132,195,196) |
| Brigatinib | ALK and EGFR TKI | 300 | ND | ND | 53% | ND | (197) |
| Lorlatmib (PF-06463922) | ALK-TKI | 100 | ND | 64 | ND | Not a P-gp substrate | (133) |
| Entrectinib | ALK-TKI | ND | ND | 43 | ND | ND | (134,198) |
(ND, not determined; NA, not available)
*
Total drug concentrations are reported