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Title: | Uncommon EGFR mutations on osimertinib, real-life data (UNICORN study): Updated results, brain efficacy, and resistance mechanisms | Authors: | Bar, Jair Peled, Nir Schokrpur, Shiruyeh Dudnik, Elizabeth Wollner, Mira Girard, Nicolas Nana, Frank Aboubakar Derijcke, Sofie Kian, Waleed Patel, Sandip P. Sorotsky, Hadas Yocheved Gantz Zer, Alona Moskovitz, Mor Metro, Giulio Rottenberg, Yakir Calles, Antonio Hochmair, Maximilian CUPPENS, Kristof Decoster, Lynn Addeo, Alfredo |
Issue Date: | 2022 | Publisher: | LIPPINCOTT WILLIAMS & WILKINS | Source: | JOURNAL OF CLINICAL ONCOLOGY, 40 (16) | Abstract: | Background: About 10% of EGFR mutations (EGFRm) are 'uncommon mutations' (ucEGFRm). osimer-tinib is a 3 rd 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 osimerti-nib. 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%. Histolo-gy was adenocarcinoma in 97%. The largest subgroups were G719X, de novo T790M and L861Q (Ta-ble). 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. Research Sponsor: AstraZeneca. | Document URI: | http://hdl.handle.net/1942/38881 | ISSN: | 0732-183X | e-ISSN: | 1527-7755 | ISI #: | 000863680302294 | Rights: | 2022 by American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. | Category: | M | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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