TP53 Mutational Status and Cetuximab Benefit in Rectal Cancer: 5-Year Results of the EXPERT-C Trial
Open Access
- 23 June 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 106 (7)
- https://doi.org/10.1093/jnci/dju121
Abstract
In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging–defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found ( P < .05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS .This publication has 25 references indexed in Scilit:
- p53 Modulates Acquired Resistance to EGFR Inhibitors and RadiationCancer Research, 2011
- Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trialThe Lancet, 2011
- Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation StatusJournal of Clinical Oncology, 2011
- Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysisThe Lancet Oncology, 2010
- TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapyBritish Journal of Cancer, 2009
- P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximabCancer Gene Therapy, 2009
- K-rasMutations and Benefit from Cetuximab in Advanced Colorectal CancerThe New England Journal of Medicine, 2008
- Impact of mutant p53 functional properties onTP53mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 databaseHuman Mutation, 2007
- Activation of p53-Dependent Growth Suppression in Human Cells by Mutations in PTEN or PIK3CAMolecular and Cellular Biology, 2007
- Chromosome 17 Deletions and p53 Gene Mutations in Colorectal CarcinomasScience, 1989