Role of osimertinib plus brain radiotherapy versus osimertinib single therapy in EGFR-mutated non-small-cell lung cancer with brain metastases: A meta-analysis and systematic review

Crit Rev Oncol Hematol. 2025 Jan:205:104540. doi: 10.1016/j.critrevonc.2024.104540. Epub 2024 Oct 30.

Abstract

Single-agent osimertinib has improved outcomes in EGFR-mutated lung cancer patients with brain metastases (BMs), but still, 40 % of them will experience an intracranial progression. We performed a systematic review to evaluate the role of brain radiotherapy upfront plus osimertinib. We evaluated articles comparing the use of osimertinib versus osimertinib plus brain radiotherapy. We included 897 patients from nine retrospective studies. Patients treated with combination therapy had an improvement in intracranial progression-free survival (HR 0.76; 95 % CI 0.61-0.94) and overall survival (HR 0.56; 95 % CI 0.36-0.87) with an acceptable safety profile. Osimertinib with upfront brain radiotherapy may be a suitable first-line treatment option for EGFR mutated patients with BMs at diagnosis. The main limitations of this analysis are the retrospective nature and the inability to control for a single variable of interest. Despite that, the combination of osimertinib and upfront brain radiotherapy is a treatment strategy that deserves further prospective trials.

Keywords: Brain metastases; Brain radiotherapy; Meta-analysis; Non small cell lung cancer; Osimertinib; Targeted therapy.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Acrylamides* / administration & dosage
  • Acrylamides* / therapeutic use
  • Aniline Compounds* / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / secondary
  • Brain Neoplasms* / therapy
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Chemoradiotherapy / methods
  • ErbB Receptors* / antagonists & inhibitors
  • ErbB Receptors* / genetics
  • Humans
  • Indoles
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Mutation*
  • Pyrimidines

Substances

  • osimertinib
  • Aniline Compounds
  • Acrylamides
  • ErbB Receptors
  • EGFR protein, human
  • Antineoplastic Agents
  • Indoles
  • Pyrimidines