Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies
Issued Date
2023-01-01
Resource Type
ISSN
17762596
eISSN
1776260X
Scopus ID
2-s2.0-85146382618
Pubmed ID
36652172
Journal Title
Targeted Oncology
Volume
18
Issue
1
Start Page
9
End Page
24
Rights Holder(s)
SCOPUS
Bibliographic Citation
Targeted Oncology Vol.18 No.1 (2023) , 9-24
Suggested Citation
Popat S., Ahn M.J., Ekman S., Leighl N.B., Ramalingam S.S., Reungwetwattana T., Siva S., Tsuboi M., Wu Y.L., Yang J.C.H. Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies. Targeted Oncology Vol.18 No.1 (2023) , 9-24. 24. doi:10.1007/s11523-022-00941-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82334
Title
Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies
Author's Affiliation
National Taiwan University Hospital
Guangdong General Hospital
Peter Maccallum Cancer Centre
The Royal Marsden Hospital
University of Melbourne
Karolinska Universitetssjukhuset
SKKU School of Medicine
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Karolinska Institutet
National Cancer Center Hospital East
The Institute of Cancer Research
Ontario Cancer Institute University of Toronto
Emory University School of Medicine
Guangdong General Hospital
Peter Maccallum Cancer Centre
The Royal Marsden Hospital
University of Melbourne
Karolinska Universitetssjukhuset
SKKU School of Medicine
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Karolinska Institutet
National Cancer Center Hospital East
The Institute of Cancer Research
Ontario Cancer Institute University of Toronto
Emory University School of Medicine
Other Contributor(s)
Abstract
Central nervous system (CNS) metastases are common in non-small-cell lung cancer (NSCLC) and associated with poor prognosis and high disease burden. Effective options are needed to treat CNS metastases, and delay or prevent their formation. For epidermal growth factor receptor mutation-positive (EGFRm) advanced NSCLC and brain metastases, upfront EGFR-tyrosine kinase inhibitors (TKIs) are recommended by the joint European Association of Neuro-Oncology–European Society for Medical Oncology and experts. While early-generation EGFR-TKIs have limited CNS efficacy, the third-generation, irreversible, EGFR-TKI osimertinib has potent efficacy in NSCLC CNS metastases. This review discusses the CNS data of osimertinib in the context of therapeutic strategies and future prospects based on expert review of published literature and relevant clinical, real-world, and ongoing studies in this setting. Osimertinib penetrates the blood–brain barrier and achieves greater exposure in the brain compared with other EGFR-TKIs. Osimertinib has demonstrated CNS efficacy, including in leptomeningeal metastases, in EGFRm advanced disease. In EGFRm stage IB–IIIA NSCLC, adjuvant osimertinib reduced CNS disease recurrence versus placebo. The burden and poor prognosis of CNS metastases necessitate more therapeutic options for their management and reduced risk of recurrence in patients with EGFRm NSCLC. Clinical studies are ongoing in advanced disease to investigate osimertinib combinations with chemotherapy/radiation therapy and optimal treatment post-CNS progression with osimertinib. Further prospective research evaluating treatments using CNS-specific endpoints and evaluating CNS resistance is needed to improve outcomes for patients with CNS metastases.