Abstract
Non-small cell lung cancer patients with brain metastases have a multitude of treatment options, but there is currently no international and multidisciplinary consensus concerning their optimal treatment. Local therapies have the principal role, especially in symptomatic patients. Advances in surgery and radiation therapy manage considerable local control. Systemic treatments have shown effect in clinical trials and in real life clinical settings; yet, at present, this is restricted to patients with asymptomatic or stable intracranial lesions. Targeted agents can have a benefit only in patients with EGFR mutations or ALK rearrangement. Immunotherapy has shown impressive results in patients with PD-L1 expression in tumor cells. Its effects can be further enhanced by a synergy with radiotherapy, possibly by increasing the percentage of responders. The present review summarizes the need for more effective systemic treatments, so that the increased intracranial control achieved by local treatments can be translated in an increase in overall survival.
Highlights
Lung cancer remains the leading cause of cancer death, with 53% of new lung cancer diagnoses being metastatic, when the 5-year relative survival rate is only 5% [1,2,3]
Ramucirumab, a VEGFR-2 monoclonal antibody, is FDA approved for the second-line treatment of metastatic NSCLC in combination with docetaxel on the findings of REVEL trial that did not exclude patients with stable previously treated central nervous system (CNS) metastases, but no data has been published on this subgroup [85]
In the AURA 3 trial, osimertinib was more effective than the doublet pemetrexed-platinum in second-line treatment for epidermal growth factor receptor (EGFR) T790M positive patients progressing on another EGFR tyrosinekinase inhibitors (TKIs), including patients with CNS stable disease [90, 91]
Summary
Lung cancer remains the leading cause of cancer death, with 53% of new lung cancer diagnoses being metastatic, when the 5-year relative survival rate is only 5% [1,2,3]. According to an update of the graded prognostic assessment (GPA) for lung cancer using molecular markers (Lung-molGPA) the median survival of patients with BMs based on a database of patients. In the population of patients diagnosed between 1979 and 1993 which formed the database for the recursive partitioning analysis (RPA) in the seminal paper of Gaspar et al the median survival ranged from 2 to 7 months [18]. In regard to BMs, immunotherapy has shown efficacy in brain tumors, as have targeted therapies with TKIs, in selected subgroups. Their importance for the majority of patients with BMs, has to be put in perspective of an significant progress in local treatments, surgery, and radiation therapy
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