Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ therapeutic use
Carcinoma, Non-Small-Cell Lung
/ drug therapy
ErbB Receptors
/ antagonists & inhibitors
Exons
/ genetics
Female
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Mutation
/ genetics
Neoplasm Staging
Protein Kinase Inhibitors
/ therapeutic use
Retrospective Studies
Survival Analysis
Treatment Outcome
Complex mutations
Exon 18
Exon 20
Lung cancer
Tyrosine kinase inhibitors
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
21
09
2018
revised:
30
10
2018
accepted:
11
11
2018
pubmed:
20
12
2018
medline:
27
6
2019
entrez:
20
12
2018
Statut:
ppublish
Résumé
Molecular characterization of non-small-cell lung cancer (NSCLC), defined predictive and druggable mutations that greatly modified patient prognoses. The most frequent driver mutations detected in NSCLC are epidermal growth factor receptor (EGFR) mutations, accounting for approximately 90% of exon 19 deletions and exon 21 point mutations. The other EGFR mutations are classified as uncommon or nonclassical and include exon 18 point mutations, exon 20 insertions, and combined mutations, which present different sensitivity to tyrosine kinase inhibitor (TKI) targeting. We collected data from EGFR TKI-naive patients with metastatic NSCLC, harboring EGFR exon 18 mutations and EGFR combined mutations treated with first- or second-generation EGFR TKIs. Efficacy end points were evaluated considering the activity of EGFR TKIs in exon 18 versus double-mutation EGFR groups. Eighty-eight patients harboring uncommon EGFR mutations were evaluated in our analysis, and subdivided into 2 group: complex mutations (cohort A = 46 patients) and double mutations in exon 18 (cohort B = 42 patients). The results showed a median progression-free survival of 8.3 versus 12.3 months (hazard ratio [HR], 0.65; P = .06) and a median overall survival of 17.0 versus 31.0 months (HR, 0.62, P = .04) favoring the EGFR combination group. Within the combination group, no detrimental effect was associated with exon 20 mutations. Our study confirmed that EGFR exon 18 and combination mutations might be considered potentially sensitive uncommon mutations, with a similar survival compared with the well known common EGFR mutations. Comparative analysis showed that patients with complex mutations achieved longer survival compared with the exon 18 group, without correlation with the presence of exon 20 mutations.
Sections du résumé
BACKGROUND
Molecular characterization of non-small-cell lung cancer (NSCLC), defined predictive and druggable mutations that greatly modified patient prognoses. The most frequent driver mutations detected in NSCLC are epidermal growth factor receptor (EGFR) mutations, accounting for approximately 90% of exon 19 deletions and exon 21 point mutations. The other EGFR mutations are classified as uncommon or nonclassical and include exon 18 point mutations, exon 20 insertions, and combined mutations, which present different sensitivity to tyrosine kinase inhibitor (TKI) targeting.
PATIENTS AND METHODS
We collected data from EGFR TKI-naive patients with metastatic NSCLC, harboring EGFR exon 18 mutations and EGFR combined mutations treated with first- or second-generation EGFR TKIs. Efficacy end points were evaluated considering the activity of EGFR TKIs in exon 18 versus double-mutation EGFR groups.
RESULTS
Eighty-eight patients harboring uncommon EGFR mutations were evaluated in our analysis, and subdivided into 2 group: complex mutations (cohort A = 46 patients) and double mutations in exon 18 (cohort B = 42 patients). The results showed a median progression-free survival of 8.3 versus 12.3 months (hazard ratio [HR], 0.65; P = .06) and a median overall survival of 17.0 versus 31.0 months (HR, 0.62, P = .04) favoring the EGFR combination group. Within the combination group, no detrimental effect was associated with exon 20 mutations.
CONCLUSION
Our study confirmed that EGFR exon 18 and combination mutations might be considered potentially sensitive uncommon mutations, with a similar survival compared with the well known common EGFR mutations. Comparative analysis showed that patients with complex mutations achieved longer survival compared with the exon 18 group, without correlation with the presence of exon 20 mutations.
Identifiants
pubmed: 30563752
pii: S1525-7304(18)30301-2
doi: 10.1016/j.cllc.2018.11.005
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Kinase Inhibitors
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e186-e194Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.