title: Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study.
abstract: Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC).
  
  
  
  This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004-2010) and National Health Insurance (2004-2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure).
  
  
  
  A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08-1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18-1.78, P = .0003).
  
  
  
  Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Rd, Taipei, 10002, Taiwan.|National Taiwan University Cancer Center, Taipei, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Rd, Taipei, 10002, Taiwan.|National Taiwan University Cancer Center, Taipei, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Shao
authors.affiliation: Center for Comparative Effectiveness Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ho-Min
authors.initials: HM
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Rd, Taipei, 10002, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Rd, Taipei, 10002, Taiwan.|Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Zhong-Zhe
authors.initials: ZZ
authors.lastname: Lin
authors.affiliation: Center for Comparative Effectiveness Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan.|Taiwan Cancer Registry, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Shu
authors.initials: MS
authors.lastname: Lai
authors.affiliation: Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Rd, Taipei, 10002, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.affiliation: Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Rd, Taipei, 10002, Taiwan. khyeh@ntu.edu.tw.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan. khyeh@ntu.edu.tw.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. khyeh@ntu.edu.tw.
authors.forename: Kun-Huei
authors.initials: KH
authors.lastname: Yeh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016879:Salvage Therapy; D015996:Survival Rate; D013624:Taiwan; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: Cetuximab; Colorectal cancer; KRAS wild-type; Predictive biomarker; Primary tumor site