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

Autor:	Yang JCH; National Taiwan University Hospital, Taipei, Republic of China., Kim SW; Asan Medical Center, Seoul, Republic of Korea., Kim DW; Seoul National University Hospital, Seoul, Republic of Korea., Lee JS; Seoul National University Bundang Hospital, Seongnam, Republic of Korea., Cho BC; Yonsei University College of Medicine, Seoul, Republic of Korea., Ahn JS; Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Lee DH; Asan Medical Center, Seoul, Republic of Korea., Kim TM; Seoul National University Hospital, Seoul, Republic of Korea., Goldman JW; University of California Los Angeles, Los Angeles, CA., Natale RB; Cedars-Sinai Medical Center, Los Angeles, CA., Brown AP; AstraZeneca, Cambridge, United Kingdom., Collins B; AstraZeneca, Cambridge, United Kingdom., Chmielecki J; AstraZeneca, Waltham, MA., Vishwanathan K; National Taiwan University Hospital, Taipei, Republic of China.; AstraZeneca, Waltham, MA., Mendoza-Naranjo A; AstraZeneca, Cambridge, United Kingdom., Ahn MJ; Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Feb 20; Vol. 38 (6), pp. 538-547. Date of Electronic Publication: 2019 Dec 06.
DOI:	10.1200/JCO.19.00457
Abstrakt:	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.
Databáze:	MEDLINE
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