Genetic profiling of cell-free DNA from cerebrospinal fluid: opening the barrier to leptomeningeal metastasis in EGFR-mutant NSCLC

Over the past decade, remarkable progress has been made in the management of advanced non-small-cell lung cancer (NSCLC), when tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors have been added to the therapeutic armamentarium. Indeed, dramatic responses to epidermal growth factor receptor (EGFR)-TKIs are observed in patients with NSCLC harbouring activating EGFR driver mutations [1, 2]. Unfortunately, all tumours ultimately develop secondary resistance, half of these due to the acquirement of the gatekeeper EGFR T790M mutation [3]. Fortunately, T790M-induced resistance can now be successfully addressed by use of third-generation EGFR-TKIs that show impressive activity in these patients [4].