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Radiation therapy plus osimertinib vs osimertinib alone in epidermal growth factor receptor mutated non-small cell lung cancer: A systematic review
Mubeena Javed, Maham Fatima, Muhammad Bari Hassan, Sanjeet Kumar, Raja Pawan, Vikram Singh, Kheentesh Kumar, Rabia Amir, Ali Karim, Inshal Jawed, Farah Alam, Danaish Kumar, Rahul Rai, Hersh Tilokani, Syed Ali Farhan Abbas Rizvi
Mubeena Javed, Department of Medicine, Allama Iqbal Medical College, Lahore 54600, Punjab, Pakistan
Maham Fatima, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, United States
Muhammad Bari Hassan, Raja Pawan, Vikram Singh, Kheentesh Kumar, Ali Karim, Rahul Rai, Department of Medicine, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Sindh, Pakistan
Sanjeet Kumar, Department of Medicine, Bilawal Medical College, Affiliated with Liaquat University of Medical and Health Sciences, Jamshoro 76090, Sindh, Pakistan
Rabia Amir, Department of Medicine, Jinnah Sindh Medical University, Karachi 75510, Sindh, Pakistan
Inshal Jawed, Department of Medicine, Dow University of Health Sciences, Karachi 75350, Sindh, Pakistan
Farah Alam, Department of Medicine, DOW Medical College, Karachi 75280, Sindh, Pakistan
Danaish Kumar, Department of Medicine, Karachi Dental and Medical College, Karachi 75600, Sindh, Pakistan
Hersh Tilokani, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
Syed Ali Farhan Abbas Rizvi, Department of Medicine, Jinnah Medical and Dental College, Karachi 74800, Sindh, Pakistan
Co-first authors: Mubeena Javed and Maham Fatima.
Author contributions: Javed M, Fatima M, Bari Hassan M, Kumar S, Pawan R, Singh V, Kumar K, Amir R, Karim A, Jawed I, Alam F, Kumar D, Rai R, Tilokani H, Abbas Rizvi SAF designed the research study; Javed M, Fatima M, Kumar S, Pawan R, Singh V, Kumar K, Amir R, Karim A, Jawed I, Alam F, Kumar D, Rai R, Abbas Rizvi SAF performed the research; Javed M, Fatima M, Kumar S, Pawan R, Singh V, Kumar K, Amir R, Karim A, Jawed I, Alam F, Kumar D, Rai R, Tilokani H, Abbas Rizvi SAF analyzed the data and wrote the manuscript; All authors have read and approved the final manuscript; Javed M and Fatima M contributed equally to this work in study design, research execution, and manuscript preparation.
Conflict-of-interest statement: All authors declare no conflicts of interest or financial interests related to the content of this manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Inshal Jawed, Chief Physician, Senior Researcher, Department of Medicine, Dow University of Health Sciences, Baba-e-urdu Karachi, Karachi 75350, Sindh, Pakistan.
inshaljwd@gmail.com
Received: May 27, 2025
Revised: July 3, 2025
Accepted: October 15, 2025
Published online: June 20, 2026
Processing time: 331 Days and 12.7 Hours
BACKGROUND
About 25%-40% of people with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) experience brain metastases, which cause major challenges in their treatment. There continues to be no agreement on the ideal method for using EGFR- tyrosine kinase inhibitors (TKIs) and radiotherapy in management.
AIM
To systematically assess how effective and safe EGFR-TKIs are when used together with or without radiotherapy in people with EGFR mutation and brain metastases.
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a complete literature search was initiated. We selected studies of two designs: Randomized trials and observational studies, which focused on therapies like EGFR-TKIs, radiotherapy, or approaches that combine both. Results for primary outcomes focused on how long people lived without the cancer spreading, whether the brain tumor shrank, and how safe the treatment was.
RESULTS
Ten randomized controlled trials and 17 observational studies, totaling 14955 patients, met the inclusion criteria. Osimertinib and similar third-generation EGFR-TKIs performed better in the brain, helping patients with central nervous system (CNS) responses of 60% to 91%. Treatment involving combined EGFR-TKI medicine and radiotherapy worked better for local control and survival than EGFR-TKI treatment alone, mainly in patients with less than three brain metastases, ECOG 0-2, and moderate to severe neurological symptoms. Cognitive function was preserved better in those who received stereotactic radiosurgery and EGFR-TKIs than in those who had whole-brain radiation therapy.
CONCLUSION
Third-generation EGFR-TKIs have good CNS effects in EGFR-mutated NSCLC. Treatments that include radiotherapy are sometimes used together, and choosing the right method depends on the amount of cancer, its effect on the person, and patient factors, which includes brain metastases (e.g., > 3), performance status (e.g., ECOG 0-2), and severity of the symptom (e.g., moderate to severe neurological symptoms).
Core Tip: The appearance of brain metastases in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer makes therapy harder. A review of 27 studies involving 14955 patients shows that osimertinib and other third-generation EGFR tyrosine kinase inhibitors achieve higher activity inside the brain and produce better responses than earlier drugs. Those with multiple brain metastases who are treated with combined radiation therapy and osimertinib do better than those treated with osimertinib alone. Cognitive function is better preserved by stereotactic radiosurgery than whole-brain radiotherapy, all while giving the same good results in managing tumors, backing individualized methods linked to the disease and patient profile.
