UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN)

Jair Bar*, Nir Peled, Shiruyeh Schokrpur, Mirjana Wolner, Ofer Rotem, Nicolas Girard, Frank Aboubakar Nana, Sofie Derijcke, Waleed Kian, Sandip Patel, Hadas Gantz-Sorotsky, Alona Zer, Mor Moskovitz, Giulio Metro, Yakir Rottenberg, Antonio Calles, Maximilian Hochmair, Kristof Cuppens, Lynn Decoster, Martin ReckDror Limon, Estelamari Rodriguez, Christoforos Astaras, Adrienne Bettini, Simon Häfliger, Alfredo Addeo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 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. 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 = 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. 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.

Original languageEnglish
Pages (from-to)169-180
Number of pages12
JournalJournal of Thoracic Oncology
Volume18
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • Compound mutations
  • Metastatic
  • NSCLC
  • Uncommon EGFR mutation

Fingerprint

Dive into the research topics of 'UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN)'. Together they form a unique fingerprint.

Cite this