421P - EGFR mutation analysis for prospective patient (pt) selection in AURA3 Phase III trial of osimertinib vs platinum-pemetrexed (plt-pem) in pts with...

Date 18 November 2017
Event ESMO Asia 2017 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Personalised Medicine
Presenter Hiroaki Akamatsu
Citation Annals of Oncology (2017) 28 (suppl_10): x124-x143. 10.1093/annonc/mdx671
Authors H. Akamatsu1, A. Delmonte2, T. John3, W. Su4, J. Lee5, G. Chang6, X. Huang7, S. Jenkins8, S. Dearden8, Y. Wu9
  • 1Department Of Internal Respiratory And Oncology, Wakayama Medical University Hospital, 641-8510 - Wakayama/JP
  • 2Oncology Unit, Istituto Romagnolo per lo Studio e la Cura dei Tumori, 47014 - Meldola/IT
  • 3Department Of Medical Oncology And Olivia Newton-john Cancer Research Institute, Austin Health, Melbourne/AU
  • 4Department Of Oncology, National Cheng Kung University Hospital, 701 - Tainan/TW
  • 5Department Of Hematology/oncology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 463-707 - Seongnam/KR
  • 6Division Of Chest Medicine, Department Of Internal Medicine, School of Medicine, National Yang-Ming University, Taipei/TW
  • 7Biostatistics And Informatics, AstraZeneca, Cambridge/GB
  • 8Personalised Healthcare And Biomarkers, Astrazeneca, Cambridge/GB
  • 9Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN



Osimertinib is a third-generation, central nervous system active, EGFR-TKI selective for both EGFR-TKI sensitising (EGFRm) and EGFR T790M resistance mutations. In AURA3, osimertinib treatment provided significant clinical benefit vs plt-pem in pts with T790M positive advanced NSCLC, whose tumours had progressed on previous EGFR-TKI therapy (Mok et al. N Engl J Med 2017;376:629–640). Pt screening for AURA3 included EGFR mutation analysis from a tissue biopsy taken following disease progression on first-line EGFR-TKI. The following retrospective analysis investigated EGFR mutation rates in screened pts.


For AURA3 screening, tumour tissue samples were centrally tested for EGFR mutations using the cobas® EGFR Mutation Test. T790M positive status was a key inclusion criteria for AURA3. Other inclusion criteria included: ≥18 years, locally-advanced or metastatic NSCLC, radiological disease progression following first-line EGFR-TKI, WHO performance status 0/1.


A total of 851 pts provided tumour samples that were tested for EGFR mutations. 820 (96%) had a valid EGFR mutation result, of which 452 (55%) were T790M positive (Table 1). T790M and Exon 19 deletion rates were similar between Asian and non-Asian pts. A higher proportion of Asian pts harboured L858R (p = 0.0017). Additional data on co-occurring mutations will be presented.Table: 421P

EGFR tissue mutations detected by central cobas test (pts with a valid cobas test result)

Number (%) of patients
T790M detectedExon 19 deletion detectedL858R detected
Total (N = 820)452 (55)477 (58)290 (35)
Asian (n = 548)293 (53)307 (56)214 (39)
Non-Asian (n = 272)159 (58)170 (63)76 (28)

Rare EGFR mutations were reported in 28/820 (3%) pts: Exon 20 insertion (11 [1%]; as only mutation, 2 [


The T790M detection rate in screened pts for AURA3 (55%) was unaffected by ethnicity, and in line with previous studies of pts with EGFRm advanced NSCLC following disease progression on EGFR-TKI.

Clinical trial identification


Legal entity responsible for the study





H. Akamatsu: Lecture fee: Astrazeneca, Eli Lilly, Chugai, MSD, Ono Pharmaceuticals, BMS, Taiho Pharmaceuticals, and Pfizer, T. John: Honoraria for advisory boards from Astra Zeneca, Merck, Pfizer, Novartis, BMS and Roche. X. Huang: Employee of AstraZeneca, S. Jenkins: Employee of, and shareholder in, AstraZenaca, S. Dearden: Employee of, and shareholder in, AstraZeneca. Y-L. Wu: Speaker fees from AstraZeneca, Roche, Eli Lilly, Sanofi, Pfizer.

All other authors have declared no conflicts of interest.