CHIH-HSIN YANGKim, Sang-WeSang-WeKimKim, Dong-WanDong-WanKimLee, Jong-SeokJong-SeokLeeCho, Byoung ChulByoung ChulChoAhn, Jin-SeokJin-SeokAhnLee, Dae H.Dae H.LeeKim, Tae MinTae MinKimGoldman, Jonathan W.Jonathan W.GoldmanNatale, Ronald B.Ronald B.NataleBrown, Andrew P.Andrew P.BrownCollins, BarbaraBarbaraCollinsChmielecki, JuliannJuliannChmieleckiVishwanathan, KarthickKarthickVishwanathanMendoza-Naranjo, AriadnaAriadnaMendoza-NaranjoStathes Paganis2021-04-232021-04-2320200732-183Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85078829575&doi=10.1200%2fJCO.19.00457&partnerID=40&md5=e0e6e7712640ce915d01a79d8cfd9193https://scholars.lib.ntu.edu.tw/handle/123456789/557717PURPOSE 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. ? 2019 by American Society of Clinical Oncology.[SDGs]SDG3alanine aminotransferase; aspartate aminotransferase; epidermal growth factor receptor; osimertinib; zorifertinib; acrylamide derivative; aniline derivative; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; osimertinib; acne; adult; aged; alanine aminotransferase blood level; anemia; Article; aspartate aminotransferase blood level; aspiration pneumonia; asthenia; brain function; cancer patient; cancer survival; cerebrospinal fluid cytology; clinical article; constipation; controlled clinical trial; controlled study; coughing; decreased appetite; diarrhea; dizziness; drug blood level; drug cerebrospinal fluid level; drug efficacy; drug safety; drug tolerability; dry skin; fatigue; female; fever; gene mutation; headache; hearing impairment; human; hypokalemia; insomnia; leptomeningeal metastasis; leptomeningeal metastasis; lung adenocarcinoma; male; median survival time; meningeal metastasis; multicenter study; nail disease; nausea; neurologic examination; non small cell lung cancer; overall survival; paronychia; phase 1 clinical trial; pneumonia; priority journal; progression free survival; pruritus; rash; side effect; stomatitis; survival rate; treatment response; tumor cell; unspecified side effect; vomiting; carcinomatous meningitis; clinical trial; genetics; lung tumor; middle aged; mutation; non small cell lung cancer; pathology; Acrylamides; Adult; Aged; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Meningeal Carcinomatosis; Middle Aged; Mutationjournal article10.1200/JCO.19.00457318092412-s2.0-85078829575