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5-Year Results of the European EXPERT-C Trial Show Benefit of Cetuximab in TP53 Wild-Type Rectal Cancer Subgroup

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Key Points

  • The addition of cetuximab was associated with nonsignificant improvements in progression-free survival and overall survival among KRAS/BRAF wild-type and all patients.
  • The addition of cetuximab was associated with significantly better progression-free survival and overall survival among TP53 wild-type patients.

In an updated analysis of the European phase II EXPERT-C trial reported in the Journal of the National Cancer Institute, Sclafani et al found that adding cetuximab (Erbitux) to neoadjuvant capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery, and adjuvant CAPOX produced no progression-free survival or overall survival benefit in the total population of patients with high-risk locally advanced rectal cancer. However, a retrospective biomarker analysis showed significant progression-free survival and overall survival benefits in the subgroup of patients with wild-type TP53 disease.

In the trial, 164 patients with magnetic resonance imaging–defined high-risk rectal cancer were randomly assigned to neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX with or without cetuximab.

Outcome in All and KRAS/BRAF Wild-Type Patients

After a median follow-up of 63.8 months in the 90 patients with KRAS/BRAF wild-type disease, 5-year progression-free survival in the cetuximab group vs CAPOX-alone group was 75.4% vs 67.8% (hazard ratio [HR] = 0.62, P = .23), and 5-year overall survival was 84.3% vs 72.3% (HR = 0.56, P = .20). There was also no significant difference between groups in the total population for 5-year progression-free survival (69.4% vs 64.3%, HR = .77, P = .34) or overall survival (77.8% vs 68.5%, HR = 0.64, P = .13).

Outcome by TP53 Status

After a median follow-up of 65 months, there was no significant difference between the cetuximab group and the CAPOX-alone group among 75 patients with mutant TP53 in progression-free survival (HR = 1.21, P = .59) or overall survival (HR = 0.97, P = .94). However among 69 patients with wild-type TP53, cetuximab was associated with significantly greater 5-year progression-free survival (89.3% vs 65.0%, HR = 0.23, P = .02) and overall survival (92.7% vs 67.5%, HR = 0.16, P = .02).

The interaction between TP53 status and cetuximab effect was significant for both progression-free survival (P = .02) and overall survival (P = .04) and remained significant after adjustment for prognostic factors and KRAS status. The effect of cetuximab in TP53 wild-type patients was consistent across all biomarker subgroups.

The investigators noted, “Caution is necessary when interpreting the results of retrospective analyses of trials that are not powered to detect survival differences.”

David Cunningham, MD, of The Royal Marsden NHS Foundation Trust, Surrey, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by the National Institute for Health Research Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Peter Stebbings Memorial Charity, Pelican Cancer Foundation, and Merck.  For full disclosures of the study authors, visit jnci.oxfordjournals.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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