Brain metastases in oncogene-driven non-small cell lung cancer

Makoto Nishino, Kenzo Soejima, Tetsuya Mitsudomi

Research output: Contribution to journalReview article

Abstract

Molecular targeted therapies have significantly improved the treatment outcome of patients with non-small cell lung cancer (NSCLC) harboring driver gene mutations such as receptor (EGFR) or anaplastic lymphoma kinase (ALK). However, the brain is a frequent site of recurrence, and it significantly deteriorates the prognosis of these patients. Treatment strategies include surgical resection, whole-brain radiation therapy, stereotactic radiotherapy, and drug therapy depending on patient condition. First-generation EGFR/ ALK tyrosine kinase inhibitors (TKI) demonstrates only limited efficacy for intracranial lesions probably because of low penetration through the blood-brain barrier (BBB). However, newly developed TKIs with improved penetration such as osimertinib for EGFR and alectinib, ceritinib, brigatinib, or lorlatinib for ALK have demonstrated significant intracranial activity that should contribute to improved overall survival. Whole-brain radiation therapy used to be a standard of care that confers alleviation of symptom and modest survival benefit. However, it potentially causes neurological and cognitive deficits as a chronic toxicity. With the prolonged survival owing to newer generation drugs, this toxicity is becoming more relevant. Stereotactic radiotherapy is considered when there are three or fewer lesions, and the lesions are <3 cm as local control of tumor is excellent, and neurotoxicity is less. In this review, we discuss the various aspects of brain metastases occurring in NSCLC patients with driver gene mutations. We also propose a treatment algorithm for these patients.

Original languageEnglish
Pages (from-to)S298-S307
JournalTranslational Lung Cancer Research
Volume8
DOIs
Publication statusPublished - 2019 Jan 1

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Oncogenes
Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Radiotherapy
Brain
Survival
Molecular Targeted Therapy
Mutation
Standard of Care
Drug-Related Side Effects and Adverse Reactions
Blood-Brain Barrier
Protein-Tyrosine Kinases
Genes
Recurrence
Drug Therapy
Therapeutics
anaplastic lymphoma kinase
Neoplasms

Keywords

  • Brain metastases
  • Driver mutations
  • Non-small cell lung cancer (NSCLC)
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology

Cite this

Brain metastases in oncogene-driven non-small cell lung cancer. / Nishino, Makoto; Soejima, Kenzo; Mitsudomi, Tetsuya.

In: Translational Lung Cancer Research, Vol. 8, 01.01.2019, p. S298-S307.

Research output: Contribution to journalReview article

Nishino, Makoto ; Soejima, Kenzo ; Mitsudomi, Tetsuya. / Brain metastases in oncogene-driven non-small cell lung cancer. In: Translational Lung Cancer Research. 2019 ; Vol. 8. pp. S298-S307.
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