Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer

From Wiki Journal Club
Jump to navigation Jump to search
Soria JC, et al. "Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer". New England Journal of Medicine. 2018. 378(2):113-125.
PubMedFull text

[[Category:]]

Clinical Question

In patients with previously untreated EGFR-mutated advanced non-small-cell lung cancer does the use of osimertinib compared to standard EGFR-TKI treatment provide a progression-free survival benefit without increasing serious adverse events or harm?

Bottom Line

In patients with previously untreated EGFR-mutated advanced non-small-cell lung cancer (NSCLC) osimertinib treatment resulted in longer progression-free survival compared to current standard first-line therapy with a similar safety profile.

Major Points

NCCN guidelines list multiple epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib, afatinib, gefitinib, and osimertinib) as first-line therapies in the treatment of EGFR-mutated advanced NSCLC. Previous studies have shown these TKIs to be more or less equal in efficacy with similar side-effect profiles. The FLAURA investigation examined the first-line use of the third-generation EGFR-TKI osimertinib in previously untreated EGFR mutation positive advanced NSCLC and showed a significantly longer progression-free survival and median duration of response compared to either gefitinib or erlotinib while showing less grade 3 or higher adverse events. The overall survival analysis was determined not significant at the interim analysis but data are still being collected.

Guidelines

No changes to guidelines as of yet.


Design

  • International-Multicenter, Double-blind, randomized, controlled trial
  • N= 556
    • Osimertinib (n=279)
    • Standard EGFR-TKI (n=277; Gefitinib=183, Erlotinib=94)
  • Setting: 132 sites in 29 countries
  • Enrollment: December 2014 through March 2016
  • Mean follow-up:
  • Analysis: Intention-to-treat
  • Primary outcome: Duration of progression-free survival as determined by investigator assessments, according to RECIST version 1.1.

Population

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

  • Demographics: Age ## years, ## female

Interventions

Outcomes

Comparisons are GROUP 1 vs. GROUP 2.

Primary Outcomes

NAME OF OUTCOME
##% vs. ##% (HR ##; 95% CI ##-##; P=##)

Secondary Outcomes

Subgroup Analysis

Adverse Events

Criticisms

Funding

Further Reading