Influence of Concurrent Mutations on Overall Survival in EGFR-mutated Non-small Cell Lung Cancer.
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Class I Phosphatidylinositol 3-Kinases
/ genetics
DNA Mutational Analysis
Drug Resistance, Neoplasm
/ genetics
ErbB Receptors
/ antagonists & inhibitors
Female
Humans
Lung
/ pathology
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Mutation
PTEN Phosphohydrolase
/ genetics
Prognosis
Progression-Free Survival
Protein Kinase Inhibitors
/ pharmacology
Proto-Oncogene Proteins p21(ras)
/ genetics
Retrospective Studies
EGFR
NSCLC
co-mutations
concurrent mutations
osimertinib
resistance
Journal
Cancer genomics & proteomics
ISSN: 1790-6245
Titre abrégé: Cancer Genomics Proteomics
Pays: Greece
ID NLM: 101188791
Informations de publication
Date de publication:
Historique:
received:
09
05
2020
revised:
30
06
2020
accepted:
02
07
2020
entrez:
30
8
2020
pubmed:
30
8
2020
medline:
6
5
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32859638
pii: 17/5/597
doi: 10.21873/cgp.20216
pmc: PMC7472449
doi:
Substances chimiques
KRAS protein, human
0
Protein Kinase Inhibitors
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
597-603Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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