Therapeutic perspectives for brain metastases in non-oncogene addicted non-small cell lung cancer (NSCLC): Towards a less dismal future?

Risk of brain metastases (BM) affects a remarkable number of non-small cell lung cancer (NSCLC) patients, impacting on their quality of life (QoL) and prognosis. While tyrosine-kinase inhibitors (TKIs) showed interesting intracranial control rates in oncogene-addicted NSCLC, BM still represent an unmet need for the counterpart without driver gene mutations. For these patients, new treatment options include anti-angiogenic drugs and immune-checkpoint inhibitors, possibly combined with standard chemotherapy, even though the benefit on BM has not been clearly defined. A multidisciplinary team including neurosurgeons, medical and radiation oncologists is needed in order to integrate systemic and loco-regional strategies at the right time point. Ad-hoc designed clinical trials are slowly emerging for previously treated patients with uncontrolled BM. The aim of this review is to offer a detailed and updated picture of possible approaches for non oncogene-addicted NSCLC patients having BM, in order to support clinicians in their daily practice.