141TiP - AZD9291, a third generation EGFR inhibitor, versus gefitinib or erlotinib in treatment-naïve patients (pts) with advanced non-small cell lung cance...

Date 17 April 2015
Event ELCC 2015
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Suresh Ramalingam
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors S.S. Ramalingam1, Y. Rukazenkov2, K. Thomas3, J. Soria4
  • 1Hematology & Medical Oncology, Emory University Winship Cancer Institute, 30322 - Atlanta/US
  • 2Gmed Oncology, AstraZeneca, SK10 4TF - Macclesfield/UK
  • 3Biostatistics, Gmd, AstraZeneca, SK10 4TF - Macclesfield/UK
  • 4Drug Development Department, Institut Gustave Roussy, 94805 - Villejuif/FR



EGFR-TKIs are the standard of care (SoC) for first-line treatment of pts with EGFRm advanced NSCLC. Resistance to EGFR-TKIs develops over time and in ∼60% of cases results from a secondary T790M mutation. AZD9291 is an oral, potent, third generation irreversible EGFR-TKI selective for EGFRm and T790M mutations. Preliminary data demonstrated promising clinical activity and a favourable tolerability profile with AZD9291 in treatment-naïve pts with EGFRm NSCLC.

Trial design

FLAURA (NCT02296125) is a Phase III, double-blind, randomised study that will compare the efficacy and safety of AZD9291 (80 mg qd, orally) to SoC EGFR-TKI (gefitinib [250 mg QD, orally] or erlotinib [150 mg qd, orally]) in treatment-naïve pts with EGFRm advanced NSCLC. The study will recruit approximately 650 eligible pts, ≥18 years of age (≥20 in Japan), World Health Organization performance status 0–1, with pathologically confirmed advanced NSCLC, not amenable to curative surgery or radiotherapy. Tumours must harbour an Ex19del or L858R substitution mutation alone or in combination with another EGFRm, determined by local or central testing. Pts will be randomised to receive either AZD9291 or SoC EGFR-TKI in a 1:1 ratio, stratified by mutation status (Ex19del or L858R) and race (Asian versus non-Asian). The primary objective is to compare progression-free survival (PFS) for AZD9291 to SoC EGFR-TKI according to RECIST v1.1. Primary analysis of PFS is powered to detect a hazard ratio of 0.74. Secondary objectives include assessment of PFS by pre-treatment T790M mutation status and by Ex19del or L858R detectable in circulating tumour DNA, objective response rate, duration of response, disease control rate, depth of response, overall survival, and the safety and tolerability profile of AZD9291 compared with SoC EGFR-TKI. Patient-reported outcomes will be assessed as secondary and exploratory objectives. The study was opened to accrual in November 2014.

Clinical trial identification NCT02296125 (22 October 2014)


S.S. Ramalingam: Consultancy fees: AbbVie.

Y. Rukazenkov: Employee and shareholder of: AstraZeneca.

K. Thomas: Remuneration for work on study design: AstraZeneca.

J.-C. Soria: Consultancy fees: AstraZeneca, Clovis, Roche.