Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered paper session - NSCLC, metastatic

5005 - Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study


19 Oct 2018


Proffered paper session - NSCLC, metastatic


Targeted Therapy

Tumour Site


Suresh Ramalingam


S.S. Ramalingam1, Y. Cheng2, C. Zhou3, Y. Ohe4, F. Imamura5, B.C. Cho6, M. Lin7, M. Majem8, R. Shah9, Y. Rukazenkov10, A. Todd11, A. Markovets12, J.C. Barrett13, J. Chmielecki12, J. Gray14

Author affiliations

  • 1 Department Of Hematology And Medical Oncology, Winship Cancer Institute of Emory University, 30322 - Atlanta/US
  • 2 Department Of Chemistry, Jilin Provincial Cancer Hospital, Changchun/CN
  • 3 Department Of Medical Oncology, Pulmonary Hospital of Tongji University, 200433 - Shanghai/CN
  • 4 Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 5 Department Of Thoracic Oncology, Osaka International Cancer Institution, 537-8511 - Osaka/JP
  • 6 Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 7 Department Of Internal Medicine, Division Of Pulmonary And Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 83301 - Kaohsiung/TW
  • 8 Medical Oncology Department, Hospital De La Santa Creu I Sant Pau, Barcelona/ES
  • 9 Medical Oncology Department, Kent Oncology Centre, Maidstone Hospital, Maidstone and Tunbridge Wells NHS Trust, Maidstone/GB
  • 10 Global Medicines Development, AstraZeneca, SG86EE - Cambridge/GB
  • 11 Biometrics And Information Sciences, AstraZeneca, SG86EE - Cambridge/GB
  • 12 Translational Sciences, Imed Biotech Unit, AstraZeneca, Waltham/US
  • 13 Translational Sciences, Imed Biotech Unit, AstraZeneca, 2451 - Waltham/US
  • 14 Department Of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US


Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 5005


In the Phase III FLAURA study (NCT02296125), osimertinib showed superior efficacy compared with standard of care (SoC) EGFR-TKIs in patients (pts) with previously untreated EGFRm advanced NSCLC. Here, we report preliminary data on mechanisms of acquired resistance to osimertinib in pts who progressed during the FLAURA study.


Pts with previously untreated EGFRm (tissue, ex19del/L858R) advanced NSCLC (N=556) were randomised 1:1 to osimertinib 80 mg once daily (QD; n=279) or SoC EGFR‑TKI (n=277, gefitinib 250 mg QD or erlotinib 150 mg QD). Paired plasma samples were collected at baseline and following RECIST progression and/or treatment discontinuation up to March 2018. Plasma samples were analysed using next generation sequencing (NGS, Guardant Health; Guardant360 73 gene panel or Omni 500 gene panel).


In the osimertinib and SoC EGFR-TKI arms, respectively, 113/279 (41%) and 159/277 (57%) pts had experienced a progression event and/or discontinued treatment and had paired plasma samples analysed by NGS. Only pts with detectable plasma EGFRm (ex19del/L858R) at baseline were evaluable for this analysis: 91/113 (81%; osimertinib) and 129/159 (81%; SoC). In the osimertinib arm, there was no evidence of acquired EGFR T790M and the most common acquired resistance mechanism detected was MET amplification (amp; 14/91; 15%), followed by EGFR C797S mutation (6/91; 7%); other mechanisms included HER2 amp, PIK3CA and RAS mutations (2–7%). In the SoC arm, the most common resistance mechanisms were T790M mutation (60/129; 47%), MET amp (5/129; 4%) and HER2 amp (3/129; 2%).


In this paired sample preliminary analysis of a subpopulation of pts (with detectable baseline plasma EGFRm) who had experienced disease progression and/or discontinued treatment, heterogeneous resistance mechanisms were detected with first-line osimertinib, with MET amplification and EGFR C797S mutation being the most commonly observed. In line with previous analyses, T790M was acquired in approximately 50% of SoC-treated pts, and none of the osimertinib‑treated pts; no unexpected resistance mechanisms were observed in osimertinib-treated pts. Exploration into novel acquired mutations is ongoing.

Clinical trial identification


Editorial Acknowledgement

We thank Ellen Maxwell, PhD, from iMed Comms, who provided medical writing support funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines ().

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.