Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study
Open accessAbstract
PURPOSE: In this phase I study (BLOOM), osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was evaluated in patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non–small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy. PATIENTS AND METHODS: Patients with cytologically confirmed LM received osimertinib 160 mg once daily. Objectives were to assess confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and safety. Additional efficacy evaluations included changes from baseline in CSF cytology and neurologic examination. Measurable lesions were assessed by investigator according to RECIST version 1.1. LMs were assessed by neuroradiologic blinded central independent review (BICR) according to Response Assessment in Neuro-Oncology LM radiologic criteria and by investigator. RESULTS: Forty-one patients were enrolled. LM ORR and DoR by neuroradiologic BICR were 62% (95% CI, 45% to 78%) and 15.2 months (95% CI, 7.5 to 17.5 months), respectively. Overall, ORR by investigator was 41% (95% CI, 26% to 58%), and median DoR was 8.3 months (95% CI, 5.6 to 16.5 months). Median investigator-assessed PFS was 8.6 months (95% CI, 5.4 to 13.7 months) with 78% maturity; median OS was 11.0 months (95% CI, 8.0 to 18.0 months) with 68% maturity. CSF tumor cell clearance was confirmed in 11 (28%; 95% CI, 15% to 44%) of 40 patients. Neurologic function was improved in 12 (57%) of 21 patients with an abnormal assessment at baseline. The adverse event and PK profiles were consistent with previous reports for osimertinib. CONCLUSION: Osimertinib showed meaningful therapeutic efficacy in the CNS and a manageable safety profile at 160 mg once daily in patients with EGFRm NSCLC and LM.
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Osimertinib is able to effectively penetrate the blood-brain barrier, providing a good therapeutic effect on BMS in advanced NSCLC, and significantly extending progression-free survival in cases of central nervous system metastases.
“In addition, multiple studies have demonstrated that osimertinib is able to effectively penetrate the blood-brain barrier,134,135 providing a good therapeutic effect on BMS in advanced NSCLC, and significantly extending progression-free survival in cases of central nervous system (CNS) metastases.136,137”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [135]
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
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- Authors
- Yang, J. C. H., Kim, S.-W., Kim, D.-W., Lee, J.-S., Cho, B. C., Ahn, J.-S., Lee, D. H., Kim, T. M., Goldman, J. W., Natale, R. B., Brown, A. P., Collins, B., Chmielecki, J., Vishwanathan, K., Mendoza-Naranjo, A., & Ahn, M.-J.
- Affiliations
- National Taiwan University Hospital (TW)
- Asan Medical Center (KR)
- Seoul National University Hospital (KR)
- Seoul National University Bundang Hospital (KR)
- Yonsei University (KR)
- Sungkyunkwan University (KR)
- University of California, Los Angeles (US)
- Cedars-Sinai Medical Center (US)
- AstraZeneca (United Kingdom) (GB)
- AstraZeneca (United States) (US)
- AstraZeneca, Cambridge, United Kingdom
- Corresponding author
- Ahn, Myung-Ju
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2020-02-20
- Volume
- 38
- Issue
- 6
- Pages
- 538-547
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC7030895
- OpenAlex
- W2994208520
- Cited by
- 395
- References
- 37
- Citations by year
- 2026: 39 · 2025: 62 · 2024: 64 · 2023: 60 · 2022: 70 · 2021: 59 · 2020: 38 · 2019: 2
- FWCI
- 31.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- osimertinib, EGFR-mutant non-small cell lung cancer, leptomeningeal metastasis, EGFR tyrosine kinase inhibitors, third-generation EGFR tyrosine kinase inhibitors, central nervous system metastasis, neurological function, pharmacokinetics, safety, objective response rate, progression-free survival, overall survival
- MeSH terms
- Acrylamides, Adult, Aged, Aniline Compounds, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Indoles, Lung Neoplasms, Male, Middle Aged, Mutation, Pyrimidines, Meningeal Carcinomatosis, ErbB Receptors
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