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Concurrent TP53 mutations predict poor outcomes of EGFR-TKI treatments in Chinese patients with advanced NSCLC
- Source :
- Cancer Management and Research. 11:5665-5675
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
Abstract
- Purpose: The study investigated the impact of TP53 mutations on the clinical efficacy of first-generation EGFR-tyrosine kinase inhibitors (TKIs) in Chinese patients with advanced or recurrent non-small-cell lung cancer (NSCLC). Patients and methods: Tissues from 163 NSCLC patients at the Affiliated Hospital of Qingdao University were analyzed by next-generation sequencing (NGS) to determine the mutational status of EGFR and concurrent genetic alterations. TP53 mutations were evaluated in relation to baseline patient characteristics and treatment outcomes (progression-free survival [PFS], overall survival [OS], objective response rate [ORR] and disease control rate [DCR]). Results: Among 163 patients with advanced NSCLC, 77 were identified as EGFR-mutant (47.2%). Six patients who did not receive TKI treatment were excluded. Among the remaining 71 patients with EGFR genetic alterations, the frequency of pathogenic TP53 mutations was 60.6% (43/71), while other concurrent mutations were rare events. Markedly shorter median PFS (mPFS) (6.5 versus 14.0 months, P=0.025) and median OS (mOS) (28.0 versus 52.0 months, P=0.023) were observed in TP53-mut patients than in TP53-wt controls. The overall DCR and ORR of TP53-mutant patients were both lower than those of the TP53-wt cases (DCR: 76.7% versus 89.3%, P=0.160; ORR: 25% versus 28%, P=0.374). Differences in prognosis were significant, especially in the subgroup of patients with TP53 non-missense mutations, non-disruptive mutations, mutations in exon 6, mutations in exon 7 and mutations in the non-DBD region among all TP53 mutations. Conclusion: TP53 mutations reduce responsiveness to TKIs and worsen the prognosis of EGFR-mutant NSCLC patients, especially for those with non-missense mutations and non-disruptive mutations, as well as mutations in exon 6, exon 7 and non-DBD region, thus acting as an independent predictor of poor outcome in advanced NSCLC patients treated with first-generation TKI therapy. Our study also suggests that TP53 mutation might be involved in primary resistance to EGFR-TKIs in Chinese NSCLC patients.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Tp53 mutation
medicine.disease_cause
03 medical and health sciences
Egfr tki
Exon
0302 clinical medicine
Internal medicine
Medicine
Mutational status
Epidermal growth factor receptor
Clinical efficacy
Lung cancer
neoplasms
Mutation
biology
business.industry
medicine.disease
respiratory tract diseases
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
business
Subjects
Details
- ISSN :
- 11791322
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancer Management and Research
- Accession number :
- edsair.doi...........1df1e026ec6d15dcc20193bf75a794d9