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

Autor: Mehlman C; Department of Respiratory Diseases and Thoracic Oncology, APHP - Hopital Ambroise Pare, EA 4340 BECCOH, UVSQ, Paris Saclay University, Boulogne-Billancourt, France., Cadranel J; Chest Department-Thoracic Oncology Expert Center, AP-HP, Groupe Hospitalier HUEP, Hopital Tenon, Paris, France, and Sorbonne University, Paris, France., Rousseau-Bussac G; Chest Departement, Creteil Intercommunal Hospital, Créteil, France., Lacave R; Department of Solide Tumours Genetic, AP-HP, Groupe Hospitalier HUEP, Tenon Hospital, Paris, France, and Sorbonne University, Paris, France., Pujals A; Department of Pathology, Henri Mondor Hospital, AP-HP, Créteil, France., Girard N; Thorax Institute, Institute Curie and PSL University, Paris, France., Callens C; Department of Genetics, Institut Curie, Paris, France., Gounant V; Thoracic Oncology Department, University Hospital Bichat-Claude Bernard, AP-HP, Paris, France., Théou-Anton N; Genetics Department, University Hospital Bichat-Claude Bernard, AP-HP, Paris, France., Friard S; Pneumology Department, Foch Hospital, Suresnes, France., Trédaniel J; Pneumology Department, Saint-Joseph Hospital, Paris, France., Blons H; Molecular Biology Department, Georges Pompidou European Hospital, AP- HP, Paris, France and INSERM UMR-S1147, CNRS SNC 5014, Saints-Pères Research Center, Paris-Descartes University, Sorbonne Paris Cité University, Paris, France., Dujon C; Pneumology Department, André Mignot Hospital, Le Chesnay, France., Duchemann B; Oncology Department, Avicenne Hospital, AP-HP, Bobigny, France and Paris XIII University, Sorbonne Paris Cité, Paris, France and Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave Roussy Cancer Campus, Villejuif, France., Schischmanoff PO; Department of Molecular Oncogenetics, Avicenne Hospital, AP-HP, Bobigny, France and INSERM UMR U978/Paris XIII University, Sorbonne Paris Cité University, Paris, France., Chinet T; Department of Respiratory Diseases and Thoracic Oncology, APHP - Hopital Ambroise Pare, EA 4340 BECCOH, UVSQ, Paris Saclay University, Boulogne-Billancourt, France., Giroux Leprieur E; Department of Respiratory Diseases and Thoracic Oncology, APHP - Hopital Ambroise Pare, EA 4340 BECCOH, UVSQ, Paris Saclay University, Boulogne-Billancourt, France. Electronic address: etienne.giroux-leprieur@aphp.fr.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2019 Nov; Vol. 137, pp. 149-156. Date of Electronic Publication: 2019 Sep 28.
DOI: 10.1016/j.lungcan.2019.09.019
Abstrakt: Objectives: The 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 Methods: We 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.
Results: Two-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.
Conclusion: We 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.)
Databáze: MEDLINE
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