UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN)
Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts. This is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR...
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creator | Bar, Jair Peled, Nir Schokrpur, Shiruyeh Wolner, Mirjana Rotem, Ofer Girard, Nicolas Aboubakar Nana, Frank 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 Häfliger, Simon Addeo, Alfredo |
description | Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.
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 investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected.
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 = 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 mutations 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.
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. |
doi_str_mv | 10.1016/j.jtho.2022.10.004 |
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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 investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected.
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 = 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 mutations 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.
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.</description><identifier>ISSN: 1556-0864</identifier><identifier>EISSN: 1556-1380</identifier><identifier>DOI: 10.1016/j.jtho.2022.10.004</identifier><identifier>PMID: 36307041</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aniline Compounds - pharmacology ; Aniline Compounds - therapeutic use ; Brain Neoplasms - drug therapy ; Brain Neoplasms - genetics ; Compound mutations ; ErbB Receptors - genetics ; Female ; Humans ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Male ; Metastatic ; Middle Aged ; Mutation ; NSCLC ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Retrospective Studies ; Uncommon EGFR mutation</subject><ispartof>Journal of thoracic oncology, 2023-02, Vol.18 (2), p.169-180</ispartof><rights>2022 International Association for the Study of Lung Cancer</rights><rights>Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-e3431544e3835d86977bff7b527bc123813cd337406154af08bdf7f6695bbaed3</citedby><cites>FETCH-LOGICAL-c400t-e3431544e3835d86977bff7b527bc123813cd337406154af08bdf7f6695bbaed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36307041$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bar, Jair</creatorcontrib><creatorcontrib>Peled, Nir</creatorcontrib><creatorcontrib>Schokrpur, Shiruyeh</creatorcontrib><creatorcontrib>Wolner, Mirjana</creatorcontrib><creatorcontrib>Rotem, Ofer</creatorcontrib><creatorcontrib>Girard, Nicolas</creatorcontrib><creatorcontrib>Aboubakar Nana, Frank</creatorcontrib><creatorcontrib>Derijcke, Sofie</creatorcontrib><creatorcontrib>Kian, Waleed</creatorcontrib><creatorcontrib>Patel, Sandip</creatorcontrib><creatorcontrib>Gantz-Sorotsky, Hadas</creatorcontrib><creatorcontrib>Zer, Alona</creatorcontrib><creatorcontrib>Moskovitz, Mor</creatorcontrib><creatorcontrib>Metro, Giulio</creatorcontrib><creatorcontrib>Rottenberg, Yakir</creatorcontrib><creatorcontrib>Calles, Antonio</creatorcontrib><creatorcontrib>Hochmair, Maximilian</creatorcontrib><creatorcontrib>Cuppens, Kristof</creatorcontrib><creatorcontrib>Decoster, Lynn</creatorcontrib><creatorcontrib>Reck, Martin</creatorcontrib><creatorcontrib>Limon, Dror</creatorcontrib><creatorcontrib>Rodriguez, Estelamari</creatorcontrib><creatorcontrib>Astaras, Christoforos</creatorcontrib><creatorcontrib>Bettini, Adrienne</creatorcontrib><creatorcontrib>Häfliger, Simon</creatorcontrib><creatorcontrib>Addeo, Alfredo</creatorcontrib><title>UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN)</title><title>Journal of thoracic oncology</title><addtitle>J Thorac Oncol</addtitle><description>Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.
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 investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected.
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 = 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 mutations 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.
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.</description><subject>Aniline Compounds - pharmacology</subject><subject>Aniline Compounds - therapeutic use</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - genetics</subject><subject>Compound mutations</subject><subject>ErbB Receptors - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>Metastatic</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>NSCLC</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Retrospective Studies</subject><subject>Uncommon EGFR mutation</subject><issn>1556-0864</issn><issn>1556-1380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFv2yAYhtG0asm6_YEdJo7twSkYjN1plypq0khpMqXNGWH8sRHZJgUyqef98eEm7bGnj-_V870SD0LfKJlQQsXVbrKLf9wkJ3meggkh_AMa06IQGWUV-Xh6k0rwEfocwi4BBeHVJzRigpGScDpG_7Yr7brO9fh2Ptvg-0NU0bo-_MCLPoLvXzbV4qkKgB_AWwh4gI2xWuln7AxeB9uBj7a3NbY93oBqs6U1gH95paPVMKQz60NM8WpoiQn-jS-2q8V0vVldfkFnRrUBvp7mOdrObh-nd9lyPV9Mb5aZ5oTEDBhntOAcWMWKphLXZVkbU9ZFXtaa5qyiTDeMlZyIhClDqroxpRHiuqhrBQ07RxfH3r13TwcIUXY2aGhb1YM7BJmXjDAqaMUSmh9R7V0IHozce9sp_ywpkYN8uZODfDnIH7LkNh19P_Uf6g6at5NX2wn4eQQg_fKvBS-DttBraKwHHWXj7Hv9_wH3QJRM</recordid><startdate>202302</startdate><enddate>202302</enddate><creator>Bar, Jair</creator><creator>Peled, Nir</creator><creator>Schokrpur, Shiruyeh</creator><creator>Wolner, Mirjana</creator><creator>Rotem, Ofer</creator><creator>Girard, Nicolas</creator><creator>Aboubakar Nana, Frank</creator><creator>Derijcke, Sofie</creator><creator>Kian, Waleed</creator><creator>Patel, Sandip</creator><creator>Gantz-Sorotsky, Hadas</creator><creator>Zer, Alona</creator><creator>Moskovitz, Mor</creator><creator>Metro, Giulio</creator><creator>Rottenberg, Yakir</creator><creator>Calles, Antonio</creator><creator>Hochmair, Maximilian</creator><creator>Cuppens, Kristof</creator><creator>Decoster, Lynn</creator><creator>Reck, Martin</creator><creator>Limon, Dror</creator><creator>Rodriguez, Estelamari</creator><creator>Astaras, Christoforos</creator><creator>Bettini, Adrienne</creator><creator>Häfliger, Simon</creator><creator>Addeo, Alfredo</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202302</creationdate><title>UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN)</title><author>Bar, Jair ; Peled, Nir ; Schokrpur, Shiruyeh ; Wolner, Mirjana ; Rotem, Ofer ; Girard, Nicolas ; Aboubakar Nana, Frank ; 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 ; Häfliger, Simon ; Addeo, Alfredo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-e3431544e3835d86977bff7b527bc123813cd337406154af08bdf7f6695bbaed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aniline Compounds - pharmacology</topic><topic>Aniline Compounds - therapeutic use</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - genetics</topic><topic>Compound mutations</topic><topic>ErbB Receptors - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Male</topic><topic>Metastatic</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>NSCLC</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Retrospective Studies</topic><topic>Uncommon EGFR mutation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bar, Jair</creatorcontrib><creatorcontrib>Peled, Nir</creatorcontrib><creatorcontrib>Schokrpur, Shiruyeh</creatorcontrib><creatorcontrib>Wolner, Mirjana</creatorcontrib><creatorcontrib>Rotem, Ofer</creatorcontrib><creatorcontrib>Girard, Nicolas</creatorcontrib><creatorcontrib>Aboubakar Nana, Frank</creatorcontrib><creatorcontrib>Derijcke, Sofie</creatorcontrib><creatorcontrib>Kian, Waleed</creatorcontrib><creatorcontrib>Patel, Sandip</creatorcontrib><creatorcontrib>Gantz-Sorotsky, Hadas</creatorcontrib><creatorcontrib>Zer, Alona</creatorcontrib><creatorcontrib>Moskovitz, Mor</creatorcontrib><creatorcontrib>Metro, Giulio</creatorcontrib><creatorcontrib>Rottenberg, Yakir</creatorcontrib><creatorcontrib>Calles, Antonio</creatorcontrib><creatorcontrib>Hochmair, Maximilian</creatorcontrib><creatorcontrib>Cuppens, Kristof</creatorcontrib><creatorcontrib>Decoster, Lynn</creatorcontrib><creatorcontrib>Reck, Martin</creatorcontrib><creatorcontrib>Limon, Dror</creatorcontrib><creatorcontrib>Rodriguez, Estelamari</creatorcontrib><creatorcontrib>Astaras, Christoforos</creatorcontrib><creatorcontrib>Bettini, Adrienne</creatorcontrib><creatorcontrib>Häfliger, Simon</creatorcontrib><creatorcontrib>Addeo, Alfredo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of thoracic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bar, Jair</au><au>Peled, Nir</au><au>Schokrpur, Shiruyeh</au><au>Wolner, Mirjana</au><au>Rotem, Ofer</au><au>Girard, Nicolas</au><au>Aboubakar Nana, Frank</au><au>Derijcke, Sofie</au><au>Kian, Waleed</au><au>Patel, Sandip</au><au>Gantz-Sorotsky, Hadas</au><au>Zer, Alona</au><au>Moskovitz, Mor</au><au>Metro, Giulio</au><au>Rottenberg, Yakir</au><au>Calles, Antonio</au><au>Hochmair, Maximilian</au><au>Cuppens, Kristof</au><au>Decoster, Lynn</au><au>Reck, Martin</au><au>Limon, Dror</au><au>Rodriguez, Estelamari</au><au>Astaras, Christoforos</au><au>Bettini, Adrienne</au><au>Häfliger, Simon</au><au>Addeo, Alfredo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN)</atitle><jtitle>Journal of thoracic oncology</jtitle><addtitle>J Thorac Oncol</addtitle><date>2023-02</date><risdate>2023</risdate><volume>18</volume><issue>2</issue><spage>169</spage><epage>180</epage><pages>169-180</pages><issn>1556-0864</issn><eissn>1556-1380</eissn><abstract>Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.
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 investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected.
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 = 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 mutations 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.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36307041</pmid><doi>10.1016/j.jtho.2022.10.004</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aniline Compounds - pharmacology Aniline Compounds - therapeutic use Brain Neoplasms - drug therapy Brain Neoplasms - genetics Compound mutations ErbB Receptors - genetics Female Humans Lung Neoplasms - drug therapy Lung Neoplasms - genetics Male Metastatic Middle Aged Mutation NSCLC Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Retrospective Studies Uncommon EGFR mutation |
title | UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN) |
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