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Systemic Therapy for Lung Cancer Brain Metastases

  • Neuro-oncology (GJ Lesser, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Systemic therapy for brain metastases (BM) is quickly moving from conventional cytotoxic chemotherapy toward targeted therapies, that allow a disruption of driver molecular pathways. The discovery of actionable driver mutations has led to the development of an impressive number of tyrosine kinase inhibitors (TKIs), that target the epidermal growth factor receptor (EGFR) mutations, anaplastic-lymphoma-kinase (ALK) rearrangements, and other rare molecular alterations in patients bearing metastatic non-small cell lung cancer (NSCLC) in the brain, with remarkable results in terms of intracranial disease control and overall survival. Moreover, these drugs may delay the use of local therapies, such as stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT). New drugs with higher molecular specificity and ability to cross the CNS barriers (BBB, BTB and blood-CSF) are being developed. Two major issues are related to targeted therapies. First, the emergence of a resistance is a common event, and a deeper understanding of molecular pathways that are involved is critical for the successful development of effective new targeted agents. Second, an early detection of tumor progression is of utmost importance to avoid the prolongation of an ineffective therapy while changing to another drug. In order to monitor over time the treatment to targeted therapies, liquid biopsy, that allows the detection in biofluids of either circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) or exosomes, is increasingly employed in clinical trials: with respect to BM the monitoring of both blood and CSF is necessary. Also, radiomics is being developed to predict the mutational status of the BM on MRI.

For patients without druggable mutations or who do not respond to targeted agents, immunotherapy with checkpoint inhibitors is increasingly employed, alone or in combination with radiotherapy. Pseudoprogression after immunotherapy alone maybe a challenge for several months after the start of treatment, and the same is true for radionecrosis after the combination of immunotherapy and SRS. In this regard, the value of advanced MRI techniques and PET imaging for a better distinction of pseudoprogression/radionecrosis and true tumor progression is promising, but needs validation in large prospective datasets. Last, a new frontier in the near future will be chemoprevention (primary and secondary), but we need to identify among solid tumors those subgroups of patients with a higher risk of relapsing into the brain and novel drugs, active on either neoplastic or normal cells of the microenvironment, that are cooperating in the invasion of brain tissue.

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Authors and Affiliations

  1. Department of Neuro-Oncology, University and City of Health and Science Hospital, via Cherasco 15, 10126, Turin, Italy

    Alessia Pellerino MD, PhD, Francesco Bruno MD, Roberta Rudà MD & Riccardo Soffietti MD

  2. Department of Neurology, Castelfranco Veneto and Treviso Hospital, via Sant’ Ambrogio di Fiera 37, 31100, Treviso, Italy

    Roberta Rudà MD

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  1. Alessia Pellerino MD, PhD
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  2. Francesco Bruno MD
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Correspondence to Alessia Pellerino MD, PhD.

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Francesco Bruno declares that he has no conflict of interest.

Roberta Rudà declares that she has no conflict of interest.

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Pellerino, A., Bruno, F., Rudà, R. et al. Systemic Therapy for Lung Cancer Brain Metastases. Curr. Treat. Options in Oncol. 22, 110 (2021). https://doi.org/10.1007/s11864-021-00911-7

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