The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Impact of TP53 Mutations on Outcome in EGFR -Mutated Patients Treated with First-Line Tyrosine Kinase Inhibitors
Published version of a preprint
Abstract
Purpose: To analyze the impact of TP53 mutations on response to first-line tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non–small cell lung cancer (NSCLC). Experimental Design: 136 EGFR-mutated NSCLC patients receiving first-line TKIs were analyzed. TP53 mutations were evaluated in 123 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: TP53 mutations were observed in 37 (30.1%), 10 (27.0%), 6 (16.2%), 9 (24.3%), and 12 (32.4%) patients in exons 5, 6, 7, and 8, respectively. DCR was 70% in TP53-mutated patients compared with 88% in TP53-wild type (wt) patients [relative risk, RR, of disease progression: 3.17 (95% CI, 1.21–8.48), P = 0.019]. In particular, a 42% DCR was observed in patients with TP53 exon 8 mutation versus 87% in exon 8 wt patients [RR of disease progression 9.6 (2.71–36.63), P < 0.001]. Shorter median PFS and OS were observed in patients with TP53 exon 8 mutations compared with others (4.2 vs. 12.5, P = 0.058, and 16.2 vs. 32.3, P = 0.114, respectively); these differences became significant in the subgroup with EGFR exon 19 deletion (4.2 vs. 16.8, P < 0.001, and 7.6 vs. not reached, P = 0.006, respectively), HR 6.99 (95% CI, 2.34–20.87, P < 0.001) and HR 4.75 (95% CI, 1.38–16.29, P = 0.013), respectively. Conclusions: TP53 mutations, especially exon 8 mutations, reduce responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, mainly those carrying exon 19 deletions. Clin Cancer Res; 23(9); 2195–202. ©2016 AACR.
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“In keeping with a more complex genomic landscape and a larger burden of clonal or sub-clonal co-drivers, multiple clinical studies have identified TP53 co-alterations as a negative prognostic marker in EGFR-mutant LUAD and a consistent predictor of worse clinical outcomes following EGFR TKI therapy72, 73, 111–116.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [112]
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Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
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Metadata
- Authors
- Canale, M., Petracci, E., Delmonte, A., Chiadini, E., Dazzi, C., Papi, M., Capelli, L., Casanova, C., De Luigi, N., Mariotti, M., Gamboni, A., Chiari, R., Bennati, C., Calistri, D., Ludovini, V., Crinò, L., Amadori, D., & Ulivi, P.
- Affiliations
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Ospedale "Santa Maria delle Croci" di Ravenna (IT)
- Ospedale Infermi di Rimini (IT)
- 4Medical Oncology Unit, S.Maria delle Croci Hospital, Ravenna, Italy.
- 3Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
- Ospedale per gli Infermi (IT)
- Azienda Ospedaliera di Perugia (IT)
- Corresponding author
- Ulivi, Paola
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2017-04-30
- Volume
- 23
- Issue
- 9
- Pages
- 2195-2202
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2534288116
- Semantic Scholar
- 1d67fc833ce2ba30f358dc72de4e727fc1633ea0
- Cited by
- 288
- References
- 37
- Citations by year
- 2026: 21 · 2025: 26 · 2024: 26 · 2023: 31 · 2022: 38 · 2021: 45 · 2020: 52 · 2019: 25 · 2018: 20 · 2017: 4
- FWCI
- 14.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- TP53 mutation, EGFR-mutant non-small cell lung cancer, tyrosine kinase inhibitors, first-line therapy, EGFR exon 19 deletion, disease control rate, progression-free survival, overall survival, treatment response, prognostic factors, predictive biomarkers, EGFR tyrosine kinase inhibitors
- MeSH terms
- Aged, Carcinoma, Non-Small-Cell Lung, Exons, Female, Humans, Male, Middle Aged, Mutation, Prognosis, Tumor Suppressor Protein p53, Sequence Deletion, Disease-Free Survival, Protein Kinase Inhibitors, ErbB Receptors
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