• Lung Cancer · Nov 2019

    Multicenter Study

    Resistance mechanisms to osimertinib in EGFR-mutated advanced non-small-cell lung cancer: A multicentric retrospective French study.

    • Camille Mehlman, Jacques Cadranel, Gaelle Rousseau-Bussac, Roger Lacave, Anaïs Pujals, Nicolas Girard, Céline Callens, Valérie Gounant, Nathalie Théou-Anton, Sylvie Friard, Jean Trédaniel, Hélène Blons, Cécile Dujon, Boris Duchemann, Pierre Olivier Schischmanoff, Thierry Chinet, and Etienne Giroux Leprieur.
    • Department of Respiratory Diseases and Thoracic Oncology, APHP - Hopital Ambroise Pare, EA 4340 BECCOH, UVSQ, Paris Saclay University, Boulogne-Billancourt, France.
    • Lung Cancer. 2019 Nov 1; 137: 149-156.

    ObjectivesThe understanding of histo-molecular mechanisms associated with resistance to osimertinib is a critical step to define the optimal treatment strategy in advanced EGFR-mutated Non-Small-Cell-Lung-Cancer (NSCLC).Materials And MethodsWe performed a multicentric retrospective analysis on a cohort of consecutive patients treated with osimertinib for an advanced EGFR-mutated NSCLC and collected histo-molecular data from plasma and tumor samples at the time of progression. Next-generation sequencing (NGS) was performed for all samples. Best Overall Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS) and data on treatment post-progression efficacy were also collected.ResultsTwo-hundred and twenty-six patients were included from 9 Academic French Hospitals between April 2015-October 2018. Osimertinib was given in second-line or more in 219 patients (97%). Best ORR was 52% and best central nervous system ORR was 56%. Median PFS and OS were 9.5 months (IQR 4.0-17.2) and 24 months (IQR 12.4-NR) respectively. At the time of analysis, 150 patients (66%) had tumor progression. Among them, 73 contributive samples (56 tumor biopsies) were available. The most frequent molecular alterations were C797S mutation (n = 9 (13%)) and MET amplification (n = 8 (11%)). Histologic transformation occurred in 5 patients (9% of tumor biopsies). In T790M + NSCLC, loss of T790 M occurred in 68% of cases. Median PFS and OS with treatment beyond progression were 6.0 months (IQR 2.0-10.4) and 15.1 months (IQR 6.7-NR) respectively and longer in case of osimertinib continuation beyond progression.ConclusionWe confirmed the efficacy of osimertinib in patients with advanced EGFR mutation positive NSCLC. At progression, the most frequent molecular alterations were MET amplification and C797S mutation.Copyright © 2019 Elsevier B.V. All rights reserved.

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