TY - JOUR
T1 - Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC
T2 - The AURA Leptomeningeal Metastases Analysis
AU - Ahn, Myung Ju
AU - Chiu, Chao Hua
AU - Cheng, Ying
AU - Han, Ji Youn
AU - Goldberg, Sarah B.
AU - Greystoke, Alastair
AU - Crawford, Jeffrey
AU - Zhao, Yanqiu
AU - Huang, Xiangning
AU - Johnson, Martin
AU - Vishwanathan, Karthick
AU - Yates, James W.T.
AU - Brown, Andrew P.
AU - Mendoza-Naranjo, Ariadna
AU - Mok, Tony
N1 - Funding Information:
Disclosure: Dr. Ahn reports speaker fees from AstraZeneca, Merck Sharp & Dohme, Ono Pharmaceutical, Eli Lilly and Company, and Roche Holding AG and consultancy for Alpha Pharmaceutical, outside the submitted work. Dr. Chiu reports honoraria from AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, and Roche Holding AG, outside the submitted work. Dr. Han reports grants and personal fees from Roche Holding AG and Pfizer ; personal fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Eli Lilly and Company, and Novartis; grants and personal fees from Pfizer ; and grants from Ono Pharmaceutical , outside the submitted work. Dr. Goldberg reports research support from AstraZeneca, during the conduct of the study; advisory board and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Bristol-Myers Squibb, Genentech, Amgen, and Spectrum Pharmaceuticals, outside the submitted work. Dr. Greystoke reports consultancy fees and speaker fees from AstraZeneca. Dr. Crawford reports research support from AstraZeneca during the conduct of the study; consultancy for Amgen, Enzychem Lifesciences, Merck, Pfizer, Coherus BioSciences, and AstraZeneca; research support from Genentech and Helsinn Healthcare SA; and leadership roles for Beyond Spring, G1 Therapeutics, Janssen Pharmaceutica, Merrimack, Mylan, and Roche, outside the submitted work. Dr. Huang is an employee of and shareholder in AstraZeneca. Dr. Johnson is an employee of and shareholder in AstraZeneca. Dr. Vishwanathan is an employee of and shareholder in AstraZeneca. Dr. Yates is an employee of and shareholder in AstraZeneca. Dr. Brown is an employee of and shareholder in AstraZeneca. Dr. Mendoza-Naranjo is an employee of and shareholder in AstraZeneca. Dr. Mok reports a leadership position at Hutchinson China MediTech, AstraZeneca, Sanomics Limited, International Association for the Study of Lung Cancer, American Society of Clinical Oncology, and Chinese Society of Clinical Oncology; stock ownership at Hutchinson China MediTech and Sanomics Limited; grants from AstraZeneca; personal fees from Boehringer Ingelheim; grants and personal fees from Roche / Genentech , Pfizer , Eli Lilly and Company , Merck Serono, Merck Sharp & Dohme , Novartis , SFJ Pharmaceuticals, and Bristol-Myers Squibb ; personal fees from Vertex, OncoGenex Pharmaceuticals, Celgene, Ignyta, Cirina, Fishawack Facilitate, Takeda Oncology, Janssen Pharmaceutica, Hutchinson China MediTech, and GeneDecode; grants from Clovis Oncology and Xcovery LLC; and personal fees from OrigiMed, Hengrui Therapeutics, Inc., Sanofi-Aventis R&D, Yuhan Co., Ltd., prIME Oncology, Inc., Amoy Diagnostics, Loxo Oncology, Inc., ACEA Pharma, Boehringer Ingelheim, Eli Lilly and Company, Bristol-Myers Squibb, Genentech, Amgen, Spectrum Pharmaceuticals, outside the submitted work. The remaining authors declare no conflict of interest.
Funding Information:
The AURA studies ( NCT01802632 , NCT02094261 , NCT02442349 , and NCT02151981 ) were funded by AstraZeneca , the manufacturer of osimertinib. The authors thank all the patients and their families. Moreover, the authors acknowledge Robert Harrison, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice guidelines ( http://www.ismpp.org/gpp3 ).
Funding Information:
Disclosure: Dr. Ahn reports speaker fees from AstraZeneca, Merck Sharp & Dohme, Ono Pharmaceutical, Eli Lilly and Company, and Roche Holding AG and consultancy for Alpha Pharmaceutical, outside the submitted work. Dr. Chiu reports honoraria from AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, and Roche Holding AG, outside the submitted work. Dr. Han reports grants and personal fees from Roche Holding AG and Pfizer; personal fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Eli Lilly and Company, and Novartis; grants and personal fees from Pfizer; and grants from Ono Pharmaceutical, outside the submitted work. Dr. Goldberg reports research support from AstraZeneca, during the conduct of the study; advisory board and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Bristol-Myers Squibb, Genentech, Amgen, and Spectrum Pharmaceuticals, outside the submitted work. Dr. Greystoke reports consultancy fees and speaker fees from AstraZeneca. Dr. Crawford reports research support from AstraZeneca during the conduct of the study; consultancy for Amgen, Enzychem Lifesciences, Merck, Pfizer, Coherus BioSciences, and AstraZeneca; research support from Genentech and Helsinn Healthcare SA; and leadership roles for Beyond Spring, G1 Therapeutics, Janssen Pharmaceutica, Merrimack, Mylan, and Roche, outside the submitted work. Dr. Huang is an employee of and shareholder in AstraZeneca. Dr. Johnson is an employee of and shareholder in AstraZeneca. Dr. Vishwanathan is an employee of and shareholder in AstraZeneca. Dr. Yates is an employee of and shareholder in AstraZeneca. Dr. Brown is an employee of and shareholder in AstraZeneca. Dr. Mendoza-Naranjo is an employee of and shareholder in AstraZeneca. Dr. Mok reports a leadership position at Hutchinson China MediTech, AstraZeneca, Sanomics Limited, International Association for the Study of Lung Cancer, American Society of Clinical Oncology, and Chinese Society of Clinical Oncology; stock ownership at Hutchinson China MediTech and Sanomics Limited; grants from AstraZeneca; personal fees from Boehringer Ingelheim; grants and personal fees from Roche/Genentech, Pfizer, Eli Lilly and Company, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, and Bristol-Myers Squibb; personal fees from Vertex, OncoGenex Pharmaceuticals, Celgene, Ignyta, Cirina, Fishawack Facilitate, Takeda Oncology, Janssen Pharmaceutica, Hutchinson China MediTech, and GeneDecode; grants from Clovis Oncology and Xcovery LLC; and personal fees from OrigiMed, Hengrui Therapeutics, Inc., Sanofi-Aventis R&D, Yuhan Co., Ltd., prIME Oncology, Inc., Amoy Diagnostics, Loxo Oncology, Inc., ACEA Pharma, Boehringer Ingelheim, Eli Lilly and Company, Bristol-Myers Squibb, Genentech, Amgen, Spectrum Pharmaceuticals, outside the submitted work. The remaining authors declare no conflict of interest.The AURA studies (NCT01802632, NCT02094261, NCT02442349, and NCT02151981) were funded by AstraZeneca, the manufacturer of osimertinib. The authors thank all the patients and their families. Moreover, the authors acknowledge Robert Harrison, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice guidelines (http://www.ismpp.org/gpp3).
Publisher Copyright:
© 2020 International Association for the Study of Lung Cancer
PY - 2020/4
Y1 - 2020/4
N2 - Introduction: 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). Methods: 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. Results: 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. Conclusions: Patients with EGFR T790M-positive NSCLC and radiologically detected LM obtained clinical benefit from osimertinib (80 mg qd).
AB - Introduction: 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). Methods: 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. Results: 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. Conclusions: Patients with EGFR T790M-positive NSCLC and radiologically detected LM obtained clinical benefit from osimertinib (80 mg qd).
KW - EGFR mutation
KW - Leptomeningeal metastases
KW - NSCLC
KW - Osimertinib
KW - T790M
UR - https://www.scopus.com/pages/publications/85078835639
UR - https://www.scopus.com/pages/publications/85078835639#tab=citedBy
U2 - 10.1016/j.jtho.2019.12.113
DO - 10.1016/j.jtho.2019.12.113
M3 - Article
C2 - 31887431
AN - SCOPUS:85078835639
SN - 1556-0864
VL - 15
SP - 637
EP - 648
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 4
ER -
