Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C).

A. Dewdney, D. Cunningham, J. Tabernero, J. Capdevila, B. Glimelius, A. Cervantes, D. Tait, G. Brown, A. Wotherspoon, D. Gonzalez de Castro, Y.J. Chua, R. Wong, Y. Barbachano, J. Oates, I. Chau

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Abstract

PURPOSE: To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. PATIENTS AND METHODS: Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. RESULTS: One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. CONCLUSION: Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.
Original languageEnglish
Pages (from-to)1620-1627
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number14
DOIs
Publication statusPublished - 10 May 2012

Keywords

  • Adenocarcinoma
  • Adult
  • Aged
  • Analysis of Variance
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols
  • Capecitabine
  • Cetuximab
  • Chemoradiotherapy, Adjuvant
  • Colectomy
  • Combined Modality Therapy
  • Deoxycytidine
  • Disease-Free Survival
  • Female
  • Fluorouracil
  • Follow-Up Studies
  • Great Britain
  • Humans
  • Intestinal Mucosa
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Organoplatinum Compounds
  • Preoperative Care
  • Radiotherapy, Adjuvant
  • Rectal Neoplasms
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome

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