The optional approach of oncogene-addicted non-small cell lung cancer with brain metastases in the new generation targeted therapies era

Alessia Spagnuolo, Matteo Muto, Fabio Monaco, Giuseppe Colantuoni, Cesare Gridelli


In recent years, the study of the molecular characteristics of non-small cell lung cancer (NSCLC) has highlighted a specific role of some genes that represent important therapeutic targets, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS- 1) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). Patients with oncogene-addicted cancer benefit more from therapy with tyrosine kinase inhibitors (TKIs) than from chemotherapy. The brain is a preferred site for tumor spread in these patients. In addition, given greater control of extracranial disease and prolonged survival, the brain is often the first site of progression. Therefore, there is great interest in therapeutic approaches that optimize the control of intracranial disease associated with systemic drugs that, by penetrating the blood-brain barrier (BBB), may improve local control. On the latter, radiotherapy provides excellent efficacy but following the results of clinical trials with new brain penetrant drugs, the question of how and especially when to perform brain radiotherapy in patients with oncogene-addicted NSCLC remains open. Prospective studies may indicate which patients are most likely to benefit from combined use or in what sequence they will undergo systemic and radiotherapy treatment. Due to the heterogeneity of patients and the introduction of new generation TKIs, a multidisciplinary assessment for the best management of therapies in NSCLC patients with molecular driver alterations and brain metastases (BM) is required.