Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study

作者：James Chih‐Hsin 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, Andy Brown, Barbara Collins, Juliann Chmielecki, Karthick Vishwanathan, Ariadna Mendoza‐Naranjo, Myung‐Ju Ahn · 发表于：Journal of Clinical Oncology · 年份：2019 · DOI：10.1200/jco.19.00457 · 被引用次数：405 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Brain Metastases and Treatment

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%;...