Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies

Cancer. 2019 Mar 15;125(6):892-901. doi: 10.1002/cncr.31891. Epub 2018 Dec 4.


Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR-TKI-sensitizing and T790M (threonine-to-methionine substitution at codon 790)-resistance mutations. The authors present long-term follow-up data from a preplanned, pooled analysis of phase 2 studies, the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial (clincialtrials.gov identifier NCT01802632) and the AURA2 trial (NCT02094261).

Methods: Patients with centrally confirmed, T790M mutation-positive, advanced non-small cell lung cancer received osimertinib 80 mg once daily until disease progression or study discontinuation. Response was assessed by a blinded, independent, central review using Response Evaluation Criteria in Solid Tumors, version 1.1. The primary endpoint was the objective response rate.

Results: In total, 411 patients received osimertinib (second line, 129 patients; third line or later, 282 patients). At the data cutoff date of November 1, 2016, the median treatment exposure was 16.4 months (range, 0-29.7 months), the objective response rate was 66% (95% confidence interval [CI], 61%-70%), the median response duration was 12.3 months (95% CI, 11.1-13.8 months), and the median progression-free survival was 9.9 months (95% CI, 9.5-12.3 months). At the data cutoff date of May 1, 2018, 271 patients (66%) had died, and 140 patients (34%) had discontinued before death. The median overall survival was 26.8 months (95% CI, 24.0-29.1 months); and the 12-month, 24-month, and 36-month survival rates were 80%, 55%, and 37%, respectively. Grade ≥3 possibly causally related (investigator assessed) adverse events were reported in 65 patients (16%), and the most common were rash (grouped terms; 42%; grade ≥3, 1%) and diarrhea (39%; <1%).

Conclusions: This pooled analysis represents the most mature clinical trial data for osimertinib in patients with pretreated, T790M-positive, advanced non-small cell lung cancer, further establishing osimertinib as a standard of care for this patient population.

Keywords: AZD9291 First Time in Patients Ascending Dose Study (AURA); epidermal growth factor receptor (EGFR); osimertinib; pooled analysis; threonine-to-methionine mutation at codon 790 (T790M); tyrosine kinase inhibitor (TKI).

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / administration & dosage*
  • Acrylamides / therapeutic use
  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds / administration & dosage*
  • Aniline Compounds / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Drug Administration Schedule
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Mutation
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / therapeutic use
  • Survival Analysis
  • Treatment Outcome


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

Associated data

  • ClinicalTrials.gov/NCT01802632
  • ClinicalTrials.gov/NCT02094261