title: 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: OBJECTIVE
  To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Medicine, Royal Marsden Hospital, Surrey, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Dewdney
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.forename: Andres
authors.initials: A
authors.lastname: Cervantes
authors.forename: Diana
authors.initials: D
authors.lastname: Tait
authors.forename: Gina
authors.initials: G
authors.lastname: Brown
authors.forename: Andrew
authors.initials: A
authors.lastname: Wotherspoon
authors.forename: David
authors.initials: D
authors.lastname: Gonzalez de Castro
authors.forename: Yu Jo
authors.initials: YJ
authors.lastname: Chua
authors.forename: Rachel
authors.initials: R
authors.lastname: Wong
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Barbachano
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Oates
authors.forename: Ian
authors.initials: I
authors.lastname: Chau
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine; D000068818:Cetuximab; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D003082:Colectomy / Q000379:methods; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000601:surgery; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011300:Preoperative Care / Q000379:methods; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000068818:Cetuximab; D005472:Fluorouracil