Cancer Res Treat.  2018 Oct;50(4):1294-1303. 10.4143/crt.2017.512.

The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

• Huang YH
• Hsu KH
• Tseng JS
• Chen KC
• Hsu CH
• Su KY
• Chen JJ
• Chen HW
• Yu SL
• Yang TY
• Chang GC

• KMID: 2424801
• DOI: http://doi.org/10.4143/crt.2017.512

Abstract

PURPOSE
The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR-tyrosine kinase inhibitor (TKI) treatment.
MATERIALS AND METHODS
We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status.
RESULTS
A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032).
CONCLUSION
PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.

Keyword

Lung neoplasms; Adenocarcinoma; Epidermal growth factor receptor mutation; T790M; Exon 19 deletion

MeSH Terms

Adenocarcinoma*
Disease-Free Survival
Epidermal Growth Factor*
Exons
Humans
Lung Neoplasms
Lung*
Mutation Rate
Odds Ratio
Phosphotransferases
Point Mutation
Prevalence
Receptor, Epidermal Growth Factor*
Sequence Deletion
Epidermal Growth Factor
Phosphotransferases
Receptor, Epidermal Growth Factor

Figure

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  Fig. 1. The patient collection flow chart. PD, progressive disease; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.

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  Fig. 2. The association between baseline epidermal growth factor receptor (EGFR) mutation status and T790M mutation status of rebiopsy.

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  Fig. 3. The association between progression-free survival of first-line epidermal growth factor receptor-tyrosine kinase inhibitor and T790M mutation status of rebiopsy.

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  Fig. 4. (A) Progression-free survival (PFS) of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) versus T790M mutation status of rebiopsy by Kaplan-Meier survival curve analysis. (B) PFS of first-line EGFR-TKI versus T790M mutation status of rebiopsy and baseline EGFR mutation status by Kaplan-Meier survival curve analysis.

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  Fig. 5. The relationship between the duration of progression-free survival and T790M detection rate by receiver operating characteristic curve analysis. AUC, area under curve.

Reference

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