Impact of TP53 mutations on outcome in EGFR-mutated patients treated with first-line tyrosine kinase inhibitors

Matteo Canale, Elisabetta Petracci, Angelo Delmonte, Elisa Chiadini, Claudio Dazzi, Maximilian Papi, Laura Capelli, Claudia Casanova, Nicoletta De Luigi, Marita Mariotti, Alessandro Gamboni, Rita Chiari, Chiara Bennati, Daniele Calistri, Vienna Ludovini, Lucio Crinò, Dino Amadori, Paola Ulivi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2195-2202
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number9
DOIs
Publication statusPublished - May 1 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    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. (2017). Impact of TP53 mutations on outcome in EGFR-mutated patients treated with first-line tyrosine kinase inhibitors. Clinical Cancer Research, 23(9), 2195-2202. https://doi.org/10.1158/1078-0432.CCR-16-0966