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).

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.

• Authors: Alice Dewdney, David Cunningham, Josep Tabernero, Jaume Capdevila, Bengt Glimelius, Andres Cervantes, Diana Tait, Gina Brown, Andrew Wotherspoon, David Gonzalez de Castro, Yu Jo Chua, Rachel Wong, Yolanda Barbachano, Jacqueline Oates, Ian Chau
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 14 Pg. 1620-7 (May 10 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22473163 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Capecitabine
• Cetuximab
• Fluorouracil

Topics

• Adenocarcinoma (mortality, pathology, therapy)
• Adult
• Aged
• Analysis of Variance
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Capecitabine
• Cetuximab
• Chemoradiotherapy, Adjuvant (methods)
• Colectomy (methods)
• Combined Modality Therapy
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Follow-Up Studies
• Humans
• Intestinal Mucosa (surgery)
• Kaplan-Meier Estimate
• Logistic Models
• Male
• Middle Aged
• Neoadjuvant Therapy (methods)
• Neoplasm Invasiveness (pathology)
• Neoplasm Staging
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Preoperative Care (methods)
• Radiotherapy, Adjuvant
• Rectal Neoplasms (mortality, pathology, therapy)
• Risk Assessment
• Survival Analysis
• Treatment Outcome
• United Kingdom