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Title: | UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN) | Authors: | Bar, Jair Peled, Nir Schokrpur, Shiruyeh Wolner, Mirjana Rotem, Ofer Girard, Nicolas Nana, Frank Aboubakar Derijcke, Sofie Kian, Waleed Patel, Sandip Gantz-Sorotsky, Hadas Zer, Alona Moskovitz, Mor Metro, Giulio Rottenberg, Yakir Calles, Antonio Hochmair, Maximilian CUPPENS, Kristof Decoster, Lynn Reck, Martin Limon, Dror Rodriguez, Estelamari Astaras, Christoforos Bettini, Adrienne Hafliger, Simon Addeo, Alfredo |
Issue Date: | 2023 | Publisher: | ELSEVIER SCIENCE INC | Source: | Journal of Thoracic Oncology, 18 (2) , p. 169 -180 | Abstract: | Introduction: Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.Methods: This is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR inhibitor. The Response Evaluation Criteria in Solid Tumors and response assessment in neuro-oncology brain metastases brain objective response rate (ORR) were evaluated by the in-vestigators. Median progression-free survival (mPFS), me-dian overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Muta-tions found at resistance were collected.Results: A total of 60 patients were included (22 centers, nine countries), with median age of 64 years, 75% females, and 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%), and de novo Thr790Met (T790M) (15%). The ORR was 61%, mPFS 9.5 months, mDOR 17.4 months, and median overall survival 24.5 months. Regarding patients with no concurrent common mutations or T790M (group A, n 1/4 44), ORR was 60%, mPFS 8.6 months, and mDOR 11 months. For G719X, ORR was 47%, mPFS 8.8 months, and mDOR 9.1 months. For L861Q, ORR was 80%, mPFS 16 months, and mDOR 16 months. For de novo T790M, ORR was 44%, mPFS 12.7 months, and mDOR 46.2 months. Compound EGFRmut including common muta-tions had better outcome compared with only ucEGFRmut. For 13 patients with a response assessment in neuro-oncology brain metastases-evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy results were analyzed: four patients with additional EGFR mutation (C797S, D585Y, E709K), three with new TP53 mutation, one with c -Met amplification, one with PIK3CA mutation, and one with neuroendocrine transformation. Conclusions: Osimertinib was found to have an activity in ucEGFRmut with a high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest data set of its kind.(c) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). | Notes: | Bar, J (corresponding author), Chaim Sheba Med Ctr, Inst Oncol, IL-5590000 Ramat Gan, Israel. Jair.bar@sheba.gov.il |
Keywords: | California | Document URI: | http://hdl.handle.net/1942/40427 | ISSN: | 1556-0864 | e-ISSN: | 1556-1380 | DOI: | 10.1016/j.jtho.2022.10.004 | ISI #: | 000982558100001 | Rights: | 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/) | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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UNcommon EGFR Mutations_ International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN).pdf | Published version | 1.38 MB | Adobe PDF | View/Open |
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