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Scientific article
Open access
English

Influence of Concurrent Mutations on Overall Survival in EGFR-mutated Non-small Cell Lung Cancer

Published inCancer Genomics & Proteomics, vol. 17, no. 5, p. 597-603
Publication date2020
First online date2020-08-28
Abstract

Background/Aim: Non-small cell lung cancer (NSCLC) patients with activating somatic mutations in the epidermal growth factor receptor (EGFR) have better outcomes with tyrosine kinase inhibitors (TKIs) than with chemotherapy. However, even with the most effective therapies, not all patients respond. The presence of concurrent pathogenic mutations could play a role in resistance. The objective of this study was to analyze the impact of concurrent mutations in genes other than EGFR on survival outcomes of patients treated with TKIs for EGFR-mutated NSCLC.

Patients and methods: We conducted a retrospective cohort analysis of patients with advanced NSCLC treated with TKIs in our center between January 2016 and December 2019. Clinical and pathological characteristics, EGFR mutational status, presence of co-occurring genetic alterations, overall (OS) and progression-free survival (PFS) were evaluated.

Results: Of the 42 patients with advanced NSCLC harboring EGFR mutations who received TKIs in our center, 22 (52%) had no concurrent mutations, 15 (36%) had a non-pathogenic, non-resistance co-mutation, and 5 (12%) had a concurrent resistance mutation. The median OS of the global population was 14.9 months, with a shorter OS in the group harboring a concurrent resistance mutation (7.7 vs. 18.1 months, p=0.002). Concurrent mutations possibly associated with resistance were found in PIK3CA, KRAS and PTEN genes.

Conclusion: Concurrent resistance mutations in genes other than EGFR influenced the outcome of patients with NSCLC, while non-resistance mutations did not alter survival, compared to the absence of co-mutations. This evidence highlights the importance of a careful interpretation of molecular findings. The best treatment options for these patients should be studied in randomized controlled trials.

eng
Keywords
  • EGFR
  • NSCLC
  • Co-mutations
  • Concurrent mutations
  • Osimertinib
  • Resistance
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • DNA Mutational Analysis
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung / pathology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • PTEN Phosphohydrolase / genetics
  • Prognosis
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Retrospective Studies
Citation (ISO format)
CHEVALLIER, Mathieu et al. Influence of Concurrent Mutations on Overall Survival in EGFR-mutated Non-small Cell Lung Cancer. In: Cancer Genomics & Proteomics, 2020, vol. 17, n° 5, p. 597–603. doi: 10.21873/cgp.20216
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Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1109-6535
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