Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases: The BLOOM study

James C.H. Yang, Sang We Kim, Dong Wan Kim, Jong Seok Lee, Byoung Chul Cho, Jin Seok Ahn, Dae H. Lee, Tae Min Kim, Jonathan W. Goldman, Ronald B. Natale, Andrew P. Brown, Barbara Collins, Juliann Chmielecki, Karthick Vishwanathan, Ariadna Mendoza-Naranjo, Myung Ju Ahn

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158 Citations (Scopus)


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), progressionfree 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 investigatorassessed 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.

Original languageEnglish
Pages (from-to)538-547
Number of pages10
JournalJournal of Clinical Oncology
Issue number6
Publication statusPublished - 2020 Feb 20

Bibliographical note

Funding Information:
Supported by AstraZeneca (Cambridge, United Kingdom), the manufacturer of osimertinib. Writing assistance was funded by AstraZeneca in accordance with Good Publications Practice guidelines.

Publisher Copyright:
© 2019 by American Society of Clinical Oncology.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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