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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.7K

Complex epidermal growth factor receptor mutations and their responses to tyrosine kinase inhibitors in previously

Bo Zhang1, Shuyuan Wang1, Jie Qian1

  • 1Pulmonary Department, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Cancer
|March 16, 2018
PubMed
Abstract

Insights

Complex epidermal growth factor receptor (EGFR) mutations impact tyrosine kinase inhibitor (TKI) treatment effectiveness. EGFR-TKI therapy shows efficacy in most complex mutation types, except for primary drug-resistant patterns.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Complex epidermal growth factor receptor (EGFR) mutations involve two or more distinct mutations within a single tumor sample.
  • The clinical significance and treatment outcomes for patients with complex EGFR mutations remain largely unknown.

Purpose of the Study:

  • To investigate the frequency of complex EGFR mutations.
  • To evaluate the efficacy of tyrosine kinase inhibitor (TKI) treatments in patients with complex EGFR mutations.

Main Methods:

  • Retrospective analysis of 16,840 patients diagnosed with EGFR mutations between January 2011 and January 2017.
  • Focus on 187 patients (3.2%) with complex EGFR mutations, particularly those receiving first-line TKI therapy for advanced adenocarcinoma.

Main Results:

  • Objective response rates (ORR) varied by mutation type: Del-19+21L858R (75.0%), Del-19/21L858R+atypical (60.0%), double atypical (71.0%), and primary drug-resistant (8.3%).
  • Median progression-free survival (PFS) was longest for Del-19+21L858R mutations (18.2 months) and shortest for primary drug-resistant patterns (1.4 months).

Conclusions:

  • EGFR-TKI therapy is effective for Del-19+21L858R, Del-19/21L858R+atypical, and double atypical mutations.
  • Efficacy is limited in patients with primary drug-resistant complex mutations, suggesting potential benefit from first-generation TKIs for Del-19+21L858R mutations.
Keywords:
complex mutationsepidermal growth factor receptorlung adenocarcinomanon-small cell lung cancertyrosine kinase inhibitors

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