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Updated: Jul 15, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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A Meta-analysis of Randomised Controlled Trials Comparing Combination Therapy as Second-line Treatment With

Kai-Xiang Zhao1, Yan-Fang Zhang2, Lei Zheng3

  • 1Department of Thoracic Surgery.

American Journal of Clinical Oncology
|October 2, 2023
PubMed
Abstract

Insights

Combination therapy did not significantly improve outcomes for advanced non-small cell lung cancer (NSCLC) patients who failed EGFR-tyrosine kinase inhibitors. Further research is needed to optimize treatment strategies for improved survival and quality of life.

Area of Science:

  • Oncology
  • Medical Research

Background:

  • Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard for EGFR-mutated non-small cell lung cancer (NSCLC).
  • Acquired resistance to EGFR-TKIs is a significant clinical challenge, necessitating novel therapeutic strategies.
  • Combinatorial approaches are being explored to overcome resistance and improve patient survival.

Approach:

  • A systematic meta-analysis was conducted, searching major scientific databases for relevant randomized controlled trials.
  • Included studies focused on patients with advanced NSCLC who had progressed on first-line EGFR-TKI therapy.
  • Efficacy outcomes (progression-free survival, overall response rate, disease control rate) and safety (adverse events) were rigorously assessed.

Key Points:

  • The meta-analysis included 6 randomized controlled trials with 785 participants.
  • Combination therapy showed no statistically significant improvement in progression-free survival, overall response rate, or disease control rate compared to monotherapy.
  • The incidence of adverse events, including fatigue and diarrhea, was also not significantly different between combination and monotherapy groups.

Conclusions:

  • Current evidence suggests that combination therapy does not offer a significant survival or response benefit over monotherapy for advanced NSCLC patients with EGFR mutations post-first-line TKI failure.
  • Further investigation is crucial to determine optimal sequencing and combinations targeting diverse molecular alterations in NSCLC.
  • Identifying effective strategies is essential to enhance patient outcomes and quality of life.

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