Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis.


Journal

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235

Informations de publication

Date de publication:
04 2020
Historique:
received: 10 10 2019
revised: 13 12 2019
accepted: 15 12 2019
pubmed: 31 12 2019
medline: 7 1 2021
entrez: 31 12 2019
Statut: ppublish

Résumé

Osimertinib has shown promising activity in patients with leptomeningeal metastases (LMs) of EGFR-positive NSCLC at 160 mg once daily (qd) (BLOOM; NCT02228369). We report LM activity with osimertinib (80 mg qd) in a retrospective analysis of studies across the AURA program (AURA extension, AURA2, AURA17, and AURA3). Patients with EGFR T790M-positive advanced NSCLC and progression after previous EGFR-tyrosine kinase inhibitor therapy received osimertinib (80 mg qd). Patients with central nervous system (CNS) metastases (including LMs) were eligible if the lesions were neurologically asymptomatic and stable. Patients with evidence of LMs at the study entry were retrospectively included for the analysis; brain scans were assessed for radiologic LM response by neuroradiologically blinded, independent central review per the modified Response Assessment in Neuro-Oncology LM criteria. LM objective response rate, duration of response, progression-free survival, and overall survival were assessed. A longitudinal analysis was performed to investigate the relationship between changes from the baseline in non-CNS tumor sizes and LM responses at each visit of patients in AURA LM and BLOOM studies. For the 22 patients included in the analysis, LM objective response rate was 55% (95% confidence interval [CI]: 32-76). Median LM duration of response was not reached (95% CI: 2.8-not calculable [NC]). Median LM progression-free survival and overall survival were 11.1 months (95% CI: 4.6-NC) and 18.8 months (95% CI: 6.3-NC), respectively. The longitudinal analysis revealed similar non-CNS and LM responses between the patients in AURA LM and BLOOM programs. Patients with EGFR T790M-positive NSCLC and radiologically detected LM obtained clinical benefit from osimertinib (80 mg qd).

Identifiants

pubmed: 31887431
pii: S1556-0864(19)33854-7
doi: 10.1016/j.jtho.2019.12.113
pii:
doi:

Substances chimiques

Acrylamides 0
Aniline Compounds 0
Antineoplastic Agents 0
Protein Kinase Inhibitors 0
osimertinib 3C06JJ0Z2O
EGFR protein, human EC 2.7.10.1
ErbB Receptors EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

637-648

Informations de copyright

Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Auteurs

Myung-Ju Ahn (MJ)

Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: silk.ahn@samsung.com.

Chao-Hua Chiu (CH)

Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Ying Cheng (Y)

Department of Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China.

Ji-Youn Han (JY)

Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.

Sarah B Goldberg (SB)

Department of Medicine (Medical Oncology), Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut.

Alastair Greystoke (A)

Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom.

Jeffrey Crawford (J)

Solid Tumor Therapeutics Program, Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina.

Yanqiu Zhao (Y)

Respiratory Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

Xiangning Huang (X)

Late-stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.

Martin Johnson (M)

Quantitative Clinical Pharmacology, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.

Karthick Vishwanathan (K)

Quantitative Clinical Pharmacology, Research and Early Development, Oncology R&D, AstraZeneca, Waltham, Massachusetts.

James W T Yates (JWT)

Drug Metabolism and Pharmacokinetics, Modelling and Simulation, Oncology R&D, AstraZeneca, Saffron Walden, United Kingdom.

Andrew P Brown (AP)

Late-stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.

Ariadna Mendoza-Naranjo (A)

Late-stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.

Tony Mok (T)

Department of Clinical Oncology, State Key Laboratory in Translational Oncology, Chinese University of Hong Kong, Hong Kong, People's Republic of China.

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Classifications MeSH