EGFR tyrosine kinase inhibitors in the treatment of EGFR mutant NSCLC metastatic to the brain
Cet article passe en revue les travaux récents, notamment les essais de phase II, sur l'usage de gefinitib et d'erlotinib pour le traitement de patients atteints d'un cancer du poumon non à petites cellules présentant des métastases cérébrales
Brain metastases are a common and devastating consequence of disease progression in patients with non-small cell lung cancer (NSCLC). The EGFR inhibitors erlotinib and gefitinib have demonstrated efficacy in patients with NSCLC and brain metastases. The cerebrospinal fluid (CSF) exposure to these drugs is a small fraction of the plasma levels achieved with standard doses, but disruption of the blood brain barrier in the presence of central nervous system (CNS) metastases is likely to lead to locally increased drug concentration, and dose escalation to boost CSF exposure has documented clinical efficacy. The use of gefitinib and erlotinib in this setting is reviewed here including evidence from case reports, case series and single arm phase II trials. High response rates in the brain are seen in patients with EGFR mutation, or in populations where this genotype is expected. By contrast, activity in the context of documented wild type EGFR in disease metastatic to the brain is not common. These drugs may potentiate the effectiveness of radiotherapy to the brain, and their use may also delay development of disease within the brain.