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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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Afatinib After Progression on Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer

Jacqueline V Aredo1, Heather A Wakelee2, Joel W Neal2

  • 1Department of Medicine, University of California, San Francisco, CA, 94143, USA; Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Cancer Treatment and Research Communications
|December 17, 2021
PubMed
Abstract

Insights

Afatinib-containing therapy showed limited activity in patients with EGFR-mutated non-small cell lung cancer (NSCLC) after osimertinib resistance. Prior response to osimertinib may predict afatinib effectiveness.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Acquired resistance to osimertinib is common in advanced EGFR-mutated NSCLC.
  • Chemotherapy is the current standard of care after osimertinib failure.
  • The efficacy of afatinib post-osimertinib is not well-established.

Purpose of the Study:

  • To evaluate the activity of afatinib-containing therapy in patients with EGFR-mutated NSCLC who progressed on osimertinib.
  • To identify predictors of response to afatinib after osimertinib treatment.

Main Methods:

  • Retrospective analysis of 15 patients with advanced EGFR-mutated NSCLC treated with afatinib after osimertinib progression.
  • Afatinib was administered as monotherapy or in combination with cetuximab or bevacizumab.
  • Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis.

Main Results:

  • The objective response rate was 6.7% and the disease control rate was 53.3%.
  • Median PFS was 2.5 months and median OS was 7.7 months.
  • Longer PFS on prior osimertinib and achieving stable disease or partial response were associated with significantly better PFS and OS on afatinib.

Conclusions:

  • Afatinib-containing therapy demonstrated limited efficacy in this patient cohort.
  • Prior response to osimertinib may predict response to subsequent afatinib therapy.
  • Further research into osimertinib resistance mechanisms is needed to optimize subsequent treatment strategies.
Keywords:
EGFR TKIEGFR mutationafatinibcetuximabosimertinib

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