Related Experiment Video

Updated: Oct 6, 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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Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Ilaria Attili1, Antonio Passaro1, Pasquale Pisapia2

  • 1Division of Thoracic Oncology, European Institute of Oncology, IRCCS, 20141 Milan, Italy.

Current Oncology (Toronto, Ont.)
|January 20, 2022
PubMed

Insights

Compound epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are diverse. EGFR tyrosine kinase inhibitors show promise for treating these mutations, with selection guided by specific mutation profiles.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Compound epidermal growth factor receptor (EGFR) mutations are found in a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients.
  • These uncommon EGFR mutations present unique challenges in diagnosis and treatment selection.

Purpose of the Study:

  • To systematically review existing data on patients with compound EGFR mutations in NSCLC.
  • To investigate the incidence, variability, and treatment responses associated with these mutations.

Main Methods:

  • Systematic literature review of preclinical and clinical data.
  • Analysis of response rates to EGFR tyrosine kinase inhibitors (TKIs) based on different mutation combinations.

Main Results:

  • High heterogeneity in the incidence of compound EGFR mutations (4-26%) was observed, influenced by testing methods and specific mutations.
  • Excluding de novo EGFR exon 20 p.T790M, EGFR TKIs demonstrated varying response rates across different compound mutation types.
  • Data suggest good responses with first- and second-generation TKIs, afatinib, and osimertinib.

Conclusions:

  • EGFR TKIs are supported for treating compound EGFR mutations in NSCLC.
  • Individualized treatment selection is crucial, considering the distinct sensitivity profiles of accompanying EGFR mutations.
Keywords:
EGFR TKINSCLCafatinibcomplexdoubleerlotinibgefitinibosimertinibuncommon

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