Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial

Cancer Sci. 2018 Jun;109(6):1930-1938. doi: 10.1111/cas.13623. Epub 2018 May 31.


Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum-based therapy plus pemetrexed (500 mg/m2 ) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end-point was progression-free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum-pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation-positive NSCLC whose disease has progressed following first-line EGFR-TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.).

Keywords: Japanese; epidermal growth factor receptor; mutation; non-small-cell lung cancer; tyrosine kinase.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Acrylamides
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / chemically induced
  • Aniline Compounds
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asian Continental Ancestry Group / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / ethnology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Japan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Pemetrexed / administration & dosage
  • Pemetrexed / adverse effects
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Platinum / administration & dosage
  • Platinum / adverse effects
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Young Adult


  • Acrylamides
  • Aniline Compounds
  • Piperazines
  • Protein Kinase Inhibitors
  • osimertinib
  • Pemetrexed
  • Platinum
  • EGFR protein, human
  • ErbB Receptors

Associated data

  • ClinicalTrials.gov/NCT02151981