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Switching from first or second generation EGFR-TKI to osimertinib in EGFR mutation-positive NSCLC

Fumio Imamura1, Takako Inoue1, Kei Kunimasa1

  • 1Department of Thoracic Oncology, Osaka International Cancer Institute 3-1-69 Otemae, Chio-ku, Osaka 541-8567, Japan.

Lung Cancer Management
|April 30, 2020
PubMed
Abstract

Insights

Switching to osimertinib before progression showed comparable efficacy to salvage use in EGFR-TKI treatment for EGFR-mutation-positive non-small cell lung cancer (NSCLC). This strategy may benefit more patients by avoiding T790M mutation selection.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Epidermal Growth Factor Receptor (EGFR) mutations are key drivers in non-small cell lung cancer (NSCLC).
  • Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) are standard treatment for EGFR mutation-positive NSCLC.
  • Acquired resistance, often mediated by the T790M mutation, limits the long-term efficacy of first-generation EGFR-TKIs.

Purpose of the Study:

  • To evaluate the efficacy of a novel switch protocol for Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) in patients with EGFR-mutation-positive non-small cell lung cancer (NSCLC).
  • To compare the outcomes of switching to osimertinib before disease progression versus using it as salvage therapy for T790M-mediated resistance.

Main Methods:

  • Retrospective analysis of clinical records from non-small cell lung cancer (NSCLC) patients treated with sequential EGFR-TKI strategies.
  • Two treatment arms were compared: salvage osimertinib for T790M-mediated acquired resistance and switch osimertinib before disease progression.
  • Data collected included progression-free survival and time to progression on osimertinib.

Main Results:

  • Progression-free survival (PFS) on osimertinib was comparable between the salvage use and switch use groups.
  • Time from treatment initiation to progression on osimertinib was similar in both the salvage and switch strategies.
  • No significant difference in key efficacy endpoints was observed between the two sequential treatment approaches.

Conclusions:

  • Switching to osimertinib before disease progression appears to offer comparable efficacy to salvage use in EGFR-TKI treated NSCLC patients.
  • The switch strategy may potentially improve overall patient benefit by avoiding the selection pressure for the T790M resistance mutation.
  • Further prospective studies are warranted to confirm the superiority of the switch protocol in a broader patient population.
Keywords:
EGFR mutationEGFR-TKINSCLCosimertinibswitchtime to failure of strategy

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