title: Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07.
abstract: BACKGROUND
  We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC).
  
  
  METHODS
  Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC).
  
  
  RESULTS
  Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%).
  
  
  CONCLUSIONS
  The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.
authors.affiliation: Department of Medical Oncology, Gastrointestinal Tumorcenter Zurich, Zurich 8038, Switzerland. daniel.helbling@gitz.ch
authors.forename: D
authors.initials: D
authors.lastname: Helbling
authors.forename: G
authors.initials: G
authors.lastname: Bodoky
authors.forename: O
authors.initials: O
authors.lastname: Gautschi
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: F
authors.initials: F
authors.lastname: Bosman
authors.forename: B
authors.initials: B
authors.lastname: Gloor
authors.forename: R
authors.initials: R
authors.lastname: Burkhard
authors.forename: R
authors.initials: R
authors.lastname: Winterhalder
authors.forename: A
authors.initials: A
authors.lastname: Madlung
authors.forename: D
authors.initials: D
authors.lastname: Rauch
authors.forename: P
authors.initials: P
authors.lastname: Saletti
authors.forename: L
authors.initials: L
authors.lastname: Widmer
authors.forename: M
authors.initials: M
authors.lastname: Borner
authors.forename: D
authors.initials: D
authors.lastname: Baertschi
authors.forename: P
authors.initials: P
authors.lastname: Yan
authors.forename: J
authors.initials: J
authors.lastname: Benhattar
authors.forename: E O
authors.initials: EO
authors.lastname: Leibundgut
authors.forename: S
authors.initials: S
authors.lastname: Bougel
authors.forename: D
authors.initials: D
authors.lastname: Koeberle
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D059248:Chemoradiotherapy; D004252:DNA Mutational Analysis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012004:Rectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D000069287:Capecitabine; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D005472:Fluorouracil