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Bar, Jair; Peled, Nir; Schokrpur, Shiruyeh; Dudnik, Elizabeth; Wollner, Mira; Girard, Nicolas; Aboubakar Nana, Frank; Derijcke, Sofie; Kian, Waleed; Patel, Sandip P.; Gantz Sorotsky, Hadas Yocheved; Zer, Alona; Moskovitz, Mor; Metro, Giulio; Rottenberg, Yakir; Calles, Antonio; Hochmair, Maximilian; Cuppens, Kristof; Decoster, Lynn; Addeo, Alfredo

Uncommon EGFR mutations on osimertinib, real-life data (UNICORN study): Updated results, brain efficacy, and resistance mechanisms

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  • Medientyp: E-Artikel
  • Titel: Uncommon EGFR mutations on osimertinib, real-life data (UNICORN study): Updated results, brain efficacy, and resistance mechanisms
  • Beteiligte: Bar, Jair; Peled, Nir; Schokrpur, Shiruyeh; Dudnik, Elizabeth; Wollner, Mira; Girard, Nicolas; Aboubakar Nana, Frank; Derijcke, Sofie; Kian, Waleed; Patel, Sandip P.; Gantz Sorotsky, Hadas Yocheved; Zer, Alona; Moskovitz, Mor; Metro, Giulio; Rottenberg, Yakir; Calles, Antonio; Hochmair, Maximilian; Cuppens, Kristof; Decoster, Lynn; Addeo, Alfredo
  • Erschienen: American Society of Clinical Oncology (ASCO), 2022
  • Erschienen in: Journal of Clinical Oncology, 40 (2022) 16_suppl, Seite 9109-9109
  • Sprache: Englisch
  • DOI: 10.1200/jco.2022.40.16_suppl.9109
  • ISSN: 0732-183X; 1527-7755
  • Entstehung:
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  • Beschreibung: 9109 Background: About 10% of EGFR mutations (EGFRm) are ‘uncommon mutations’ (ucEGFRm). osimertinib is a 3rd generation EGFRi, active against common EGFRm. We aimed to collect real-world data about systemic and brain response and resistance mechanisms to osimertinib for ucEGFRm patients. Methods: This is a multi-center, retrospective study of ucEGFRm mNSCLC treated with osimertinib as first EGFRi. RECIST and RANO-BM response was evaluated by investigators. Progression free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated from initiation of osimertinib. Mutations found at resistance were collected. Results: 62 patients (pts) were identified in 22 centers from 9 countries. Median age was 64 (35-91) years, 74% females, 84% Caucasian, never/former/current smokers were 48%/39%/11% respectively, ECOG PS was 0-1/2/3-4 in 84%/10%/5%. Histology was adenocarcinoma in 97%. The largest subgroups were G719X, de novo T790M and L861Q (Table). Compound EGFR mutations were found in 27 pts (44%), TP53 mutations in 21 pts (34%). In 17 cases (27%), compound mutations included the common L858R/deletion19 and/or de novo T790M. Most frequent metastatic sites were lung/bone/brain in 45%/44%/39%. Most frequent toxicities were gastrointestinal (32 pts, 52%) and skin (24 pts, 39%); 8 pts had grade 3-4 AEs. No grade 5 AE occurred. 3 pts had AEs leading to discontinuation. RECIST response (RR) was available for 53 pts, CR - 4 (8%), PR - 27 (51%), SD - 17 (32%), and PD - 5 (9%). Median DOR (mDOR) was 17.4 months (95% CI 9.1-NA). mPFS was 9.5 months (95% CI 8.5–17.4). mOS was 24.5 months (95% CI 17.4-35.1). See Table for efficacy in the major subgroups. 24 pts (39%) had brain metastasis at presentation, for 12 pts a brain response by RANO-BM was available with 25%/25%/33%/17% CR/PR/SD/PD. For 14 pts, rebiopsy mutation analysis at progression on osimertinib was available: 3 pts with an additional EGFR mutation (C797S,D585Y, E709K), 3 pts with a new TP53 mutation, 1 with c-Met amplification and 1 pt with transformation to neuroendocrine carcinoma. Conclusions: Osimertinib demonstrated activity in ucEGFRm with 91% disease control rate and encouraging PFS and DOR. Brain response was seen in 50% of cases. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest dataset of osimertinib as the first EGFRi for ucEGFRm presented so far. [Table: see text]
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