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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Veröffentlicht in:Journal of thoracic oncology 2023-02, Vol.18 (2), p.169-180
Hauptverfasser: 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
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container_issue 2
container_start_page 169
container_title Journal of thoracic oncology
container_volume 18
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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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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