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Updated: Jan 23, 2026

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Outcome Differences Between First- and Second-generation EGFR Inhibitors in Advanced EGFR Mutated NSCLC in a Large

Sally C Lau1, Negar Chooback2, Cheryl Ho3

  • 1Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Clinical Lung Cancer
|June 11, 2019
PubMed
Abstract

Insights

Second-generation EGFR TKIs offer survival benefits for real-world lung cancer patients, similar to clinical trials. These treatments are a viable first-line option, particularly for younger patients with specific EGFR mutations.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Second-generation EGFR TKIs show promise over first-generation in trials but with higher toxicity.
  • Real-world data is needed to confirm survival benefits in diverse patient populations.

Purpose of the Study:

  • To compare outcomes of first-generation versus second-generation EGFR TKIs in advanced non-small-cell lung cancer (NSCLC).
  • To assess the generalizability of clinical trial findings to real-world NSCLC patient populations.

Main Methods:

  • Retrospective analysis of 484 advanced NSCLC patients treated with EGFR TKIs (2010-2015).
  • Propensity score matching and Cox proportional hazards modeling were used to adjust for patient characteristics and estimate survival.
  • Outcomes were stratified by TKI generation and specific EGFR mutation status.

Main Results:

  • Second-generation TKIs were associated with improved overall survival (HR 0.69, P=0.05), particularly in patients with EGFR exon 19 deletions.
  • No significant survival benefit was observed for second-generation TKIs in patients with the L858R mutation (HR 0.91, P=0.74).
  • Second-generation TKI use led to dose reductions in 40% of patients but discontinuation in only 1%.

Conclusions:

  • The survival benefit of second-generation EGFR TKIs observed in clinical trials is applicable to real-world NSCLC patients.
  • Second-generation TKIs represent a reasonable first-line therapy for advanced NSCLC.
  • Treatment selection favored younger patients with uncommon EGFR mutations and fewer CNS metastases for second-generation TKIs.
Keywords:
AfatinibErlotinibGefitinibReal-world populationTKI

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