Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC Journal Articles uri icon

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  • BACKGROUND: Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported. METHODS: In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point. RESULTS: The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; Pā€‰=ā€‰0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. CONCLUSIONS: Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.).


  • Juergens, Rosalyn
  • Ramalingam, Suresh S
  • Vansteenkiste, Johan
  • Planchard, David
  • Cho, Byoung Chul
  • Gray, Jhanelle E
  • Ohe, Yuichiro
  • Zhou, Caicun
  • Reungwetwattana, Thanyanan
  • Cheng, Ying
  • Chewaskulyong, Busyamas
  • Shah, Riyaz
  • Cobo, Manuel
  • Lee, Ki Hyeong
  • Cheema, Parneet
  • Tiseo, Marcello
  • John, Thomas
  • Lin, Meng-Chih
  • Imamura, Fumio
  • Kurata, Takayasu
  • Todd, Alexander
  • Hodge, Rachel
  • Saggese, Matilde
  • Rukazenkov, Yuri
  • Soria, Jean-Charles

publication date

  • January 2, 2020

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