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Clinical Management in NSCLC Patients With EGFR Mutation After Osimertinib Progression With Unknown Resistance

Xin Liao1, Tingting He2, Xiong Wan1

  • 1Department of Respiratory and Critical Care Medicine, Chongqing University Jiangjin Hospital, Chongqing, China.

The Clinical Respiratory Journal
|October 15, 2024
PubMed
Abstract

Insights

Immunotherapy plus chemotherapy shows higher response rates and longer progression-free survival in non-small cell lung cancer (NSCLC) patients progressing on osimertinib with unknown resistance mechanisms. This combination offers a promising treatment option compared to chemotherapy alone or osimertinib plus bevacizumab.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Osimertinib is a standard treatment for EGFR-mutated non-small cell lung cancer (NSCLC).
  • Mechanisms of resistance to osimertinib are unknown in nearly half of patients.
  • Optimal treatment strategies post-osimertinib progression remain controversial.

Purpose of the Study:

  • To compare the efficacy and safety of immunotherapy + chemotherapy, chemotherapy alone, and osimertinib + bevacizumab.
  • To evaluate treatment outcomes in NSCLC patients with unknown resistance mechanisms after osimertinib progression.

Main Methods:

  • Retrospective review of advanced NSCLC patients after osimertinib progression with unknown resistance mechanisms.
  • Patients were divided into three treatment groups: immunotherapy + chemotherapy, chemotherapy alone, and osimertinib + bevacizumab.
  • Comparison of clinicopathological features, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Main Results:

  • Immunotherapy + chemotherapy demonstrated a significantly higher ORR (55.56% vs. 14.81% vs. 0% for 1st line; 30.77% vs. 6.67% vs. 13.33% for 2nd/3rd line).
  • Median PFS was significantly longer in the immunotherapy + chemotherapy group (8.2 months vs. 4.0 vs. 6.0 months; p=0.0066).
  • Osimertinib + bevacizumab showed numerically longer median OS (47.6 months) and had milder adverse events, particularly gastrointestinal and bone marrow related.

Conclusions:

  • Immunotherapy + chemotherapy is a beneficial treatment for NSCLC patients progressing on osimertinib with unknown resistance mechanisms.
  • This combination offers superior ORR and PFS compared to chemotherapy or osimertinib + bevacizumab.
  • Osimertinib + bevacizumab is a viable, safer option with a numerically longer OS.
Keywords:
EGFR mutationNSCLCchemo‐immunotherapyosimertinibresistance

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