Back to Search Start Over

Impact of TP53 Mutations on Outcome in EGFR-Mutated Patients Treated with First-Line Tyrosine Kinase Inhibitors

Authors :
Laura Capelli
Rita Chiari
Elisabetta Petracci
Maximilian Papi
Dino Amadori
Daniele Calistri
Chiara Bennati
Matteo Canale
Nicoletta De Luigi
Lucio Crinò
Marita Mariotti
Claudia Casanova
Claudio Dazzi
Angelo Delmonte
Paola Ulivi
Vienna Ludovini
Elisa Chiadini
Alessandro Gamboni
Source :
Clinical Cancer Research. 23:2195-2202
Publication Year :
2017
Publisher :
American Association for Cancer Research (AACR), 2017.

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.

Details

ISSN :
15573265 and 10780432
Volume :
23
Database :
OpenAIRE
Journal :
Clinical Cancer Research
Accession number :
edsair.doi...........e8e7d344b64cfedd8b912a70b8af8751
Full Text :
https://doi.org/10.1158/1078-0432.ccr-16-0966