title: A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer.
abstract: BACKGROUND
  We assessed the treatment effect of panitumumab plus best supportive care (BSC) vs BSC on overall survival (OS) in patients with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC) and report the first prospective extended RAS analysis in a phase 3 trial.
  
  
  METHODS
  Patients with wild-type KRAS exon 2 mCRC were randomised 1 : 1 to panitumumab (6 mg kg-1Q2W) plus BSC or BSC. On-study crossover was prohibited. RAS mutation status was determined by central laboratory testing. The primary endpoint was OS in wild-type KRAS exon 2 mCRC; OS in wild-type RAS mCRC (KRAS and NRAS exons 2, 3, and 4) was a secondary endpoint.
  
  
  RESULTS
  Three hundred seventy seven patients with wild-type KRAS exon 2 mCRC were randomised. Median OS was 10.0 months with panitumumab plus BSC vs 7.4 months with BSC (HR=0.73; 95% CI=0.57-0.93; P=0.0096). RAS ascertainment was 86%. In wild-type RAS mCRC, median OS for panitumumab plus BSC was 10.0 vs 6.9 months for BSC (HR=0.70; 95% CI=0.53-0.93; P=0.0135). Patients with RAS mutations did not benefit from panitumumab (OS HR=0.99; 95% CI=0.49-2.00). No new safety signals were observed.
  
  
  CONCLUSIONS
  Panitumumab significantly improved OS in wild-type KRAS exon 2 mCRC. The effect was more pronounced in wild-type RAS mCRC, validating previous retrospective analyses.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan, Seoul 138-736, South Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.affiliation: North Estonia Medical Centre Foundation, Tallinn 13419, Estonia.
authors.forename: Anneli
authors.initials: A
authors.lastname: Elme
authors.affiliation: University Hospital Center 'Sestre Milosrdnice', Zagreb 10000, Croatia.
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Kusic
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: MEDISPROF, Cluj-Napoca 400367, Romania.
authors.forename: Anghel Adrian
authors.initials: AA
authors.lastname: Udrea
authors.affiliation: National Cancer Center, Goyang-si, Gyeonggi-do 410-769, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Yonsei University Health System Severance Hospital, Seoul 120-752, South Korea.
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Centro Medico Nacional Siglo XXI, Mexico City 06725, Mexico.
authors.forename: Ricardo Villalobos
authors.initials: RV
authors.lastname: Valencia
authors.affiliation: Dr Rai Memorial Medical Centre, Chennai 600018, India.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Klinicka bolnica Sveti Duh, Zagreb 10000, Croatia.
authors.forename: Ante
authors.initials: A
authors.lastname: Bilic
authors.affiliation: Clinic for Gastroenterology and Hepatology of Military Medical Academy of Serbia, Belgrade 11000, Serbia.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Manojlovic
authors.affiliation: Amgen Inc., Thousand Oaks, CA 91320, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.affiliation: Amgen Inc., Thousand Oaks, CA 91320, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Guan
authors.affiliation: Amgen Inc., Thousand Oaks, CA 91320, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lofton-Day
authors.affiliation: Amgen Inc., Thousand Oaks, CA 91320, USA.
authors.forename: A Scott
authors.initials: AS
authors.lastname: Jung
authors.affiliation: Department of Oncology, Center of Oncology, Clinical Hospital Center Split, Split 21000, Croatia.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vrdoljak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D003131:Combined Modality Therapy / Q000379:methods; D018592:Cross-Over Studies; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000077544:Panitumumab; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins