PMID- 18946061
OWN - NLM
STAT- MEDLINE
DCOM- 20081030
LR  - 20240103
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 359
IP  - 17
DP  - 2008 Oct 23
TI  - K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
PG  - 1757-65
LID - 10.1056/NEJMoa0804385 [doi]
AB  - BACKGROUND: Treatment with cetuximab, a monoclonal antibody directed against the 
      epidermal growth factor receptor, improves overall and progression-free survival 
      and preserves the quality of life in patients with colorectal cancer that has not 
      responded to chemotherapy. The mutation status of the K-ras gene in the tumor may 
      affect the response to cetuximab and have treatment-independent prognostic value. 
      METHODS: We analyzed tumor samples, obtained from 394 of 572 patients (68.9%) 
      with colorectal cancer who were randomly assigned to receive cetuximab plus best 
      supportive care or best supportive care alone, to look for activating mutations 
      in exon 2 of the K-ras gene. We assessed whether the mutation status of the K-ras 
      gene was associated with survival in the cetuximab and supportive-care groups. 
      RESULTS: Of the tumors evaluated for K-ras mutations, 42.3% had at least one 
      mutation in exon 2 of the gene. The effectiveness of cetuximab was significantly 
      associated with K-ras mutation status (P=0.01 and P<0.001 for the interaction of 
      K-ras mutation status with overall survival and progression-free survival, 
      respectively). In patients with wild-type K-ras tumors, treatment with cetuximab 
      as compared with supportive care alone significantly improved overall survival 
      (median, 9.5 vs. 4.8 months; hazard ratio for death, 0.55; 95% confidence 
      interval [CI], 0.41 to 0.74; P<0.001) and progression-free survival (median, 3.7 
      months vs. 1.9 months; hazard ratio for progression or death, 0.40; 95% CI, 0.30 
      to 0.54; P<0.001). Among patients with mutated K-ras tumors, there was no 
      significant difference between those who were treated with cetuximab and those 
      who received supportive care alone with respect to overall survival (hazard 
      ratio, 0.98; P=0.89) or progression-free survival (hazard ratio, 0.99; P=0.96). 
      In the group of patients receiving best supportive care alone, the mutation 
      status of the K-ras gene was not significantly associated with overall survival 
      (hazard ratio for death, 1.01; P=0.97). CONCLUSIONS: Patients with a colorectal 
      tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with 
      a tumor bearing wild-type K-ras did benefit from cetuximab. The mutation status 
      of the K-ras gene had no influence on survival among patients treated with best 
      supportive care alone. (ClinicalTrials.gov number, NCT00079066.)
CI  - 2008 Massachusetts Medical Society
FAU - Karapetis, Christos S
AU  - Karapetis CS
AD  - Flinders Medical Centre and Flinders University, Adelaide, Australia. 
      c.karapetis@flinders.edu.au
FAU - Khambata-Ford, Shirin
AU  - Khambata-Ford S
FAU - Jonker, Derek J
AU  - Jonker DJ
FAU - O'Callaghan, Chris J
AU  - O'Callaghan CJ
FAU - Tu, Dongsheng
AU  - Tu D
FAU - Tebbutt, Niall C
AU  - Tebbutt NC
FAU - Simes, R John
AU  - Simes RJ
FAU - Chalchal, Haji
AU  - Chalchal H
FAU - Shapiro, Jeremy D
AU  - Shapiro JD
FAU - Robitaille, Sonia
AU  - Robitaille S
FAU - Price, Timothy J
AU  - Price TJ
FAU - Shepherd, Lois
AU  - Shepherd L
FAU - Au, Heather-Jane
AU  - Au HJ
FAU - Langer, Christiane
AU  - Langer C
FAU - Moore, Malcolm J
AU  - Moore MJ
FAU - Zalcberg, John R
AU  - Zalcberg JR
LA  - eng
SI  - ClinicalTrials.gov/NCT00079066
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
CIN - N Engl J Med. 2008 Oct 23;359(17):1834-6. doi: 10.1056/NEJMe0806778. PMID: 
      18946069
CIN - N Engl J Med. 2009 Feb 19;360(8):833-4; author reply 835-6. doi: 
      10.1056/NEJMc082346. PMID: 19228630
CIN - N Engl J Med. 2009 Feb 19;360(8):834; author reply 835-6. PMID: 19238675
CIN - N Engl J Med. 2009 Feb 19;360(8):834; author reply 835-6. PMID: 19238676
CIN - N Engl J Med. 2009 Feb 19;360(8):834-5; author reply 835-6. PMID: 19238677
CIN - N Engl J Med. 2009 Feb 19;360(8):835; author reply 835-6. PMID: 19238678
CIN - N Engl J Med. 2009 Feb 19;360(8):835; author reply 835-6. PMID: 19238679
CIN - Nat Rev Clin Oncol. 2009 Jun;6(6):306-7. doi: 10.1038/nrclinonc.2009.69. PMID: 
      19483733
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*therapeutic use
MH  - Cetuximab
MH  - Colorectal Neoplasms/*drug therapy/genetics/mortality
MH  - DNA Mutational Analysis
MH  - Disease Progression
MH  - ErbB Receptors/antagonists & inhibitors/*immunology
MH  - Female
MH  - *Genes, ras
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Palliative Care
MH  - Quality of Life
EDAT- 2008/10/24 09:00
MHDA- 2008/10/31 09:00
CRDT- 2008/10/24 09:00
PHST- 2008/10/24 09:00 [pubmed]
PHST- 2008/10/31 09:00 [medline]
PHST- 2008/10/24 09:00 [entrez]
AID - 359/17/1757 [pii]
AID - 10.1056/NEJMoa0804385 [doi]
PST - ppublish
SO  - N Engl J Med. 2008 Oct 23;359(17):1757-65. doi: 10.1056/NEJMoa0804385.