Differential significance of molecular subtypes which were classified into EGFR exon 19 deletion on the first line afatinib monotherapy.
BMC Cancer
; 20(1): 103, 2020 Feb 06.
Article
em En
| MEDLINE
| ID: mdl-32028909
ABSTRACT
BACKGROUND:
Epidermal growth factor receptor (EGFR)-sensitizing mutation, exon 19 deletion consists of several molecular variants. Influences of these variants on clinical response to EGFR tyrosine kinase inhibitors remain elusive.METHODS:
West Japan Oncology Group 8114LTR is a prospective, multi-institutional biomarker study. Treatment naïve, advanced non-small-cell lung cancer patients with EGFR-sensitizing mutation received afatinib monotherapy. We conducted a preplanned subset analysis of patients harboring exon 19 deletion. Tumor tissue exon 19 deletion molecular variants were identified by blocking-oligo-dependent polymerase chain reaction (PCR) and by Luminex Technology. Plasma cfDNA was also obtained before and after the treatment and EGFR mutations were detected with multiplexed, pico-droplet digital PCR assay.RESULTS:
Among 57 registered patients, twenty-nine patients were exon 19 deletion. Tissue DNA and cfDNA were available in 26 patients. Among the detected seven molecular variants, the most frequent was p.E746_A750delELREA (65.4%). According to the various classifications of molecular variants, twenty one (80.8%) were classified into 15-nucleotide deletion, one (3.8%) into 18-nucleotide deletion, and four patients (15.4%) into other insertion/substitution variant subgroups. The patient subgroup with 15-nucleotide deletion showed significantly longer progression-free survival than patients in other mixed insertion/substitution variant subgroup (p = 0.0244).CONCLUSIONS:
The clinical significance of molecular variants of exon 19 deletion on the first line afatinib monotherapy is reported here for the first time. Further investigation is needed for development of better therapeutic strategies. TRIAL REGISTRATION This trial was registered at UMIN Clinical Trials Registry at 2014/12/4 (UMIN000015847).Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Éxons
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Deleção de Sequência
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Inibidores de Proteínas Quinases
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Afatinib
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article