title: Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer.
abstract: The primary analysis of the ASPECCT study demonstrated that panitumumab was non-inferior to cetuximab for overall survival (OS) in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). Here, we report the final analysis results of ASPECCT.
  
  
  
  Patients with wild-type KRAS exon 2 mCRC who progressed on or were intolerant to irinotecan- or oxaliplatin-based chemotherapy were randomised to receive panitumumab 6 mg/kg once every 2 weeks or cetuximab (400 mg/m2) followed by 250 mg/m2weekly. The primary end-point was OS assessed for non-inferiority. Patients were followed for survival for 24 months after the last patient was randomised and a final analysis was conducted. No formal hypothesis testing was done. Post hoc analyses of outcomes by prior bevacizumab exposure, worst-grade skin toxicity (0-1 versus 2-4) and worst-grade hypomagnesaemia (0 versus 1-4) were conducted.
  
  
  
  Nine hundred ninety-nine patients were randomised and received ≥1 treatment dose (panitumumab, n = 499; cetuximab, n = 500). Median OS was 10.2 months with panitumumab versus 9.9 months with cetuximab (hazard ratio = 0.94; 95% confidence interval = 0.82-1.07). Median progression-free survival was 4.2 months with panitumumab and 4.4 months with cetuximab (hazard ratio = 0.98; 95% confidence interval = 0.87-1.12). Longer OS was observed for patients with increased skin toxicity and with hypomagnesaemia in both arms. Furthermore, OS was longer for patients with prior bevacizumab exposure treated with panitumumab than with cetuximab. The observed safety profiles were consistent with previous studies.
  
  
  
  Consistent with the primary analysis, the final analysis of ASPECCT showed panitumumab was non-inferior to cetuximab for OS for patients with chemotherapy-refractory, wild-type KRAS exon 2 mCRC.
  
  
  
  ClinicalTrials.gov, NCT01001377.
authors.affiliation: The Queen Elizabeth Hospital and University of Adelaide, Woodville, SA, Australia. Electronic address: timothy.price@sa.gov.au.
authors.forename: Timothy
authors.initials: T
authors.lastname: Price
authors.affiliation: Asan Medical Center, University of Ulsan, Songpa-Gu, Seoul, South Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Fudan University Cancer Hospital, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Universita Politecnica delle Marche, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: University of Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa.
authors.forename: Paul
authors.initials: P
authors.lastname: Ruff
authors.affiliation: Apollo Hospital, Hyderabad, India.
authors.forename: Attili Satya
authors.initials: AS
authors.lastname: Suresh
authors.affiliation: Leicester Royal Infirmary, Leicester, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Thomas
authors.affiliation: N. N. Blokhin Cancer Research Center of RAMS, Moscow, Russia.
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Guan
authors.affiliation: Antwerp University Hospital, Edegem, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D000068818:Cetuximab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008274:Magnesium / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D016016:Proportional Hazards Models; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015996:Survival Rate; D014883:Water-Electrolyte Imbalance / Q000097:blood / Q000453:epidemiology; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D000068258:Bevacizumab; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D008274:Magnesium; D000068818:Cetuximab
keywords: Anti-EGFR therapy; Colorectal cancer; Gastrointestinal cancer; Panitumumab