title: Randomized phase II study of cetuximab versus irinotecan and cetuximab in patients with chemo-refractory KRAS codon G13D metastatic colorectal cancer (G13D-study).
abstract: OBJECTIVE
  This study investigated the efficacy and safety of cetuximab-based treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D mutation.
  
  
  METHODS
  An assessment of the efficacy and safety of cetuximab-based treatment was performed in an observation-enriched randomized controlled study comparing the cetuximab alone group (Cet group) and the combination of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated mCRC in Japan. In this study, the patients received a biweekly (500 mg/m2on day 1) or weekly (250 mg/m2) intravenous infusion of cetuximab in Cet group, or a biweekly (500 mg/m2on day 1) or weekly (250 mg/m2) intravenous infusion of cetuximab followed by irinotecan (150 mg/m2) in CetI group. Propensity score adjustment was used to achieve balance in the observational arm.
  
  
  RESULTS
  Data from a total of 29 patients (10 in Cet group, 19 in CetI group) were analyzed. Crude median progression-free survival time was 2.9 months in the Cet group and 2.5 months in the CetI group. Crude disease control rates were 55.6% in the Cet group and 47.4% in the CetI group. After a median follow-up of 43 months, the crude median overall survival was 8.0 months in the Cet group and 7.6 months in the CetI group. Cetuximab-based treatment did not markedly increase any characteristic toxicity and was generally well tolerated. Propensity score analyses adjusted for performance status and number of metastases showed comparable results with the crude results.
  
  
  CONCLUSIONS
  Cetuximab-based treatment seemed to benefit patients with chemotherapy-resistant, refractory KRAS G13D-mutated mCRC. Our results might support the administration of cetuximab-based treatment for KRAS-mutant mCRC and would be able to provide treatment flexibility in this setting.
authors.affiliation: Aizawa Comprehensive Cancer Center, Aizawa Hospital, Nagano, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan. aoyamat@kcch.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Aoyama
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Clinical Oncology, Kagawa University Faculty of Medicine, Kagawa, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Cancer biology, University of Hawaii Cancer Center, Honolulu, USA.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Takinishi
authors.affiliation: Department of Gastrointestinal Surgery, Nakadori General Hospital, Akita, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shindo
authors.affiliation: Department of Surgery, Tokai Central Hospital, Kakamigahara, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Biostatistics, The University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Cancer Center, Aichi Medical University, Nagakute, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage / Q000627:therapeutic use*; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D003062:Codon; C117307:KRAS protein, human; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002166:Camptothecin
keywords: Cetuximab; Colorectal cancer; KRAS G13D