In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 4_suppl ( 2011-02-01), p. 426-426
Abstract:
426 Background: Anti-EGFR antibodies are more efficient when EGFR pathway is activated without mutations on downstream effectors such as KRAS and BRAF (Lievre et al. Cancer Res. 2008 and Khambata-Ford et al. J Clin Oncol. 2007). Moreover, tumor growth from EGFR activation may required inactivation of the molecular brake p53 suggesting that anti-EGFR therapy should be more efficient if p53 is inactivated (Oden-Gangloff et al. Br J Cancer. 2008). The aim of the study was to evaluate, in an independent series, the impact of p53 mutations in irinotecan-refractory KRAS wt-BRAF wt MCRC patients treated with anti- EGFR. Methods: A total of 100 MCRC patients treated with cetuximab-based CT were included. KRAS and BRAF mutational status were determined using SNaPshot or allelic discrimination methods. TP53 mutations within exons 5 to 8 were detected using direct sequencing. Response to cetuximab, based on RECIST criteria, was evaluated according to molecular analysis using the Fischer exact test. Progression- free survivals (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared with log-rank test. Results: Objective response (OR = partial and complete response) was observed in 40% and control disease (CD = OR+stable disease) in 74% of patients. Median PFS and OS was 12 weeks and 12 months, respectively. TP53 mutations were detected in 66% of patients and were not significantly associated with OR and CD. In contrast, patients with KRAS wt-BRAF wt and TP53 mutation had significantly longer PFS as compared to KRAS wt–BRAF wt and TP53 non mutated patients (32 weeks vs. 21 weeks, respectively; p = 0.01). There was a trend but not significant increased OS in patients with TP53 mutations (16 months vs. 13 months) Conclusions: In this independent study, our results confirm that TP53 mutation was significantly associated with an increase PFS in irinotecan-refrcatory KRAS wt-BRAF wt MCRC patients treated with anti-EGFR. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2011.29.4_suppl.426
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2011
detail.hit.zdb_id:
2005181-5
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