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Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis.
J Thorac Oncol. 2020 04; 15(4):637-648.JT

Abstract

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).

Authors+Show Affiliations

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.Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.Department of Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China.Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.Department of Medicine (Medical Oncology), Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut.Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom.Solid Tumor Therapeutics Program, Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina.Respiratory Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.Late-stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.Quantitative Clinical Pharmacology, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.Quantitative Clinical Pharmacology, Research and Early Development, Oncology R&D, AstraZeneca, Waltham, Massachusetts.Drug Metabolism and Pharmacokinetics, Modelling and Simulation, Oncology R&D, AstraZeneca, Saffron Walden, United Kingdom.Late-stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.Late-stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.Department of Clinical Oncology, State Key Laboratory in Translational Oncology, Chinese University of Hong Kong, Hong Kong, People's Republic of China.

Pub Type(s)

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

Language

eng

PubMed ID

31887431

Citation

Ahn, Myung-Ju, et al. "Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: the AURA Leptomeningeal Metastases Analysis." Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, vol. 15, no. 4, 2020, pp. 637-648.
Ahn MJ, Chiu CH, Cheng Y, et al. Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis. J Thorac Oncol. 2020;15(4):637-648.
Ahn, M. J., Chiu, C. H., Cheng, Y., Han, J. Y., Goldberg, S. B., Greystoke, A., Crawford, J., Zhao, Y., Huang, X., Johnson, M., Vishwanathan, K., Yates, J. W. T., Brown, A. P., Mendoza-Naranjo, A., & Mok, T. (2020). Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, 15(4), 637-648. https://doi.org/10.1016/j.jtho.2019.12.113
Ahn MJ, et al. Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: the AURA Leptomeningeal Metastases Analysis. J Thorac Oncol. 2020;15(4):637-648. PubMed PMID: 31887431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: 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, Y1 - 2019/12/27/ PY - 2019/10/10/received PY - 2019/12/13/revised PY - 2019/12/15/accepted PY - 2019/12/31/pubmed PY - 2019/12/31/medline PY - 2019/12/31/entrez KW - EGFR mutation KW - Leptomeningeal metastases KW - NSCLC KW - Osimertinib KW - T790M SP - 637 EP - 648 JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JO - J Thorac Oncol VL - 15 IS - 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). SN - 1556-1380 UR - https://www.unboundmedicine.com/medline/citation/31887431/Osimertinib_for_Patients_With_Leptomeningeal_Metastases_Associated_With_EGFR_T790M_Positive_Advanced_NSCLC:_The_AURA_Leptomeningeal_Metastases_Analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1556-0864(19)33854-7 DB - PRIME DP - Unbound Medicine ER -
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