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M. Canale
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-006 - Role of TP53 Mutations in Determining Primary Resistance to First-Line Tyrosine Kinase Inhibitors in EGFR-Mutated NSCLC Patients (ID 3861)
14:30 - 14:30 | Author(s): M. Canale
- Abstract
Background:
Patients with non-small-cell lung cancer (NSCLC) carrying specific mutations at epidermal growth factor receptor (EGFR) gene are usually sensitive to treatments with tyrosine kinase inhibitors (TKIs). However, not all EGFR-mutated patients respond equally to TKI treatments, and approximately 20-30% show primary resistance. Although the mechanisms responsible for acquired resistance are known, those responsible for primary resistance are not completely understood. In this study we aimed to assess the role of TP53 mutations in a cohort of advanced EGFR-mutated NSCLC patients receiving first-line TKIs. We analyzed TP53 gene status in relation to outcome in terms of overall response rate, disease control rate (DCR), response duration, progression free survival (PFS) and overall survival (OS).
Methods:
We retrospectively analyzed 136 patients with advanced EGFR-mutated NSCLC treated with first-line TKIs from January 2012 to April 2015. Exons 5-8 of TP53 gene were amplified by PCR and sequenced by direct sequencing on 123 patients. DCR was defined as the sum of complete response, partial response and stable disease. The survival endpoints examined were PFS and OS. PFS was defined as the time from start of first-line treatment to disease progression or death, whichever occurred first. OS was defined as the time from start of first-line treatment to death.
Results:
TP53 mutations were observed in 37 (30.1%) patients:10 (27.0%), 6 (16.2%), 9 (24.3%) and 12 (32.4%) in exons 5, 6, 7 and 8, respectively. DCR was 70% in TP53-mutated patients compared to 88% in TP53-wt patients (relative risk, RR: 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 compared to 87% in exon 8 wt patients (RR 9.6 [2.71-36.63], p<0.001). Shorter median PFS and OS were observed in patients with TP53 exon 8 mutations compared to other patients (4.2 months vs 12.5 months [p=0.058] and 16.2 months vs 32.3 months [p=0.114], respectively); these differences became significant in the subgroup of patients with EGFR exon 19 deletion (4.2 months vs 16.8 months [p<0.001] and 7.6 months vs not reached [p=0.006], respectively), hazard ratio (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.
Conclusion:
TP53 mutations, in particular exon 8 mutations and those defined as nondisruptive, reduce responsiveness to TKI treatment and induce a worse prognosis in EGFR-mutated NSCLC patients, especially in those carrying exon 19 deletions.
