Management of brain metastases from lung cancer in the era of immunotherapy: a review of the literature

The brain is one of the most frequent sites of metastases in lung cancer patients, whose prognosis is related to the histological, biomolecular and clinical features of the disease. Over the years, the survival has improved significantly with the introduction of immune checkpoint inhibitors (ICIs), but there are limited data concerning their efficacy in patients with brain metastases. The aim of this review is to describe the biological mechanisms supporting the use of immunotherapy for brain metastases and the outcomes experienced by lung cancer patients with brain involvement enrolled in Phase III registration trials of ICIs. We also review retrospective data on ICIs alone or combined with brain radiotherapy, and indicate future directions for preclinical and clinical research. Lay abstract Patients with lung cancer may develop brain metastases during the course of their disease. In fact, the brain is one of the organs at higher risk of metastases, which have a significant impact on survival. The treatment of lung cancer patients has notably improved after the introduction of immune checkpoint inhibitors, but there are limited data concerning their efficacy in patients with brain metastases. The aim of this article is to describe the biological mechanisms supporting the use of immunotherapy for brain metastases and its impact on improvement of patients' symptoms and survival. We also present data on possible combinations of immunotherapy and local treatments as radiotherapy, that represent one of the most promising strategies to treat lung tumors.