Is there any opportunity for immune checkpoint inhibitor therapy in non-small cell lung cancer patients with brain metastases?

Although brain metastases occur in almost one-third of non-small cell lung cancer (NSCLC) patients, and immune checkpoint inhibitors (ICI) either as monotherapy or combined with chemotherapy are the new standard of care in the first line setting, most trials excluded patients with asymptomatic and/ or untreated brain metastases. Brain metastases have a major clinical impact due to the worsening of the patient's prognosis and quality of life. Furthermore, the incidence of brain metastases is increasing in NSCLC patients, due to a longer survival and better imaging techniques. Therefore, brain metastases are increasingly becoming a research topic. Recent clinical data endorses ICI as a therapeutic strategy in this subpopulation of NSCLC patients, although the immune environment in brain metastases is more immune ignorant compared with the microenvironment in the primary tumour or in the extracranial metastases. In this review we summarize the current evidence of ICI strategy in NSCLC patients with brain metastases, including trial and real-life data. We also state that the different tumor microenvironment between brain metastases and primary tumor may explain the discordance on the response rate during treatment with ICI. Last, we focus on future directions, including the role and optimal sequence of cranial irradiation and ICI, prognostic scores, the best response assessment and new imaging techniques.