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

F. Sclafani, D. Gonzalez, D. Cunningham, S. Hulkki Wilson, C. Peckitt, J. Tabernero, B. Glimelius, A. Cervantes, A. Dewdney, Andrew Wotherspoon, Gina Brown, D. Tait, J. Oates, I. Chau

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34 Citations (Scopus)

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.
Original languageEnglish
JournalJ Natl Cancer Inst
Volume106
Issue number7
DOIs
Publication statusPublished - Jul 2014

Keywords

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols
  • 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
  • Odds Ratio
  • Radiotherapy, Adjuvant
  • Randomized Controlled Trials as Topic
  • Rectal Neoplasms
  • Retrospective Studies
  • Risk Factors
  • Sample Size
  • Tumor Suppressor Protein p53

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  • Cite this

    Sclafani, F., Gonzalez, D., Cunningham, D., Hulkki Wilson, S., Peckitt, C., Tabernero, J., Glimelius, B., Cervantes, A., Dewdney, A., Wotherspoon, A., Brown, G., Tait, D., Oates, J., & Chau, I. (2014). TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial. J Natl Cancer Inst, 106(7). https://doi.org/10.1093/jnci/dju121