TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial.

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.

• Authors: Francesco Sclafani, David Gonzalez, David Cunningham, Sanna Hulkki Wilson, Clare Peckitt, Josep Tabernero, Bengt Glimelius, Andrés Cervantes, Alice Dewdney, Andrew Wotherspoon, Gina Brown, Diana Tait, Jacqueline Oates, Ian Chau
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 106 Issue 7 (Jul 2014) ISSN: 1460-2105 [Electronic] United States
• PMID: 24957073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• TP53 protein, human
• Tumor Suppressor Protein p53
• Cetuximab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cetuximab
• Chemotherapy, Adjuvant
• Clinical Trials, Phase II as Topic
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Mutation
• Neoadjuvant Therapy (methods)
• Odds Ratio
• Radiotherapy, Adjuvant
• Randomized Controlled Trials as Topic
• Rectal Neoplasms (drug therapy, genetics, pathology, surgery)
• Retrospective Studies
• Risk Factors
• Sample Size
• Tumor Suppressor Protein p53 (genetics)