Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials.
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Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. / Bokemeyer, Carsten; Eric, Van Cutsem; Rougier, Philippe; Ciardiello, Fortunato; Heeger, Steffen; Schlichting, Michael; Celik, Ilhan; Köhne, Claus-Henning.
in: EUR J CANCER, Jahrgang 48, Nr. 10, 10, 01.07.2012, S. 1466-1475.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials.
AU - Bokemeyer, Carsten
AU - Eric, Van Cutsem
AU - Rougier, Philippe
AU - Ciardiello, Fortunato
AU - Heeger, Steffen
AU - Schlichting, Michael
AU - Celik, Ilhan
AU - Köhne, Claus-Henning
N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.
PY - 2012/7/1
Y1 - 2012/7/1
N2 - BACKGROUND: The CRYSTAL and OPUS randomised clinical trials demonstrated that adding cetuximab to first-line chemotherapy in patients with KRAS wild-type metastatic colorectal cancer (mCRC) significantly improved treatment outcome compared with chemotherapy alone. The objective of this pooled analysis was to further investigate these findings in patients with KRAS wild-type tumours using extended survival data and following an enhancement in the ascertainment rate of KRAS and BRAF tumour mutation status from these studies.METHODS: Pooled individual patient data from each study were analysed for overall survival (OS), progression-free survival (PFS) and best overall response rate (ORR) in patients evaluable for KRAS and BRAF mutation status. Treatment arms were compared according to mutation status using log-rank and Cochran-Mantel-Haenszel tests.RESULTS: In 845 patients with KRAS wild-type tumours adding cetuximab to chemotherapy led to a significant improvement in OS (hazard ratio [HR] 0.81; p=0.0062), PFS (HR 0.66; p<0.001) and ORR (odds ratio 2.16; p<0.0001). BRAF mutations were detected in 70/800 evaluable tumours. No significant differences were found in outcome between the treatment groups in these patients. Prognosis was worse in each treatment arm for patients with BRAF tumour mutations compared with those with BRAF wild-type tumours.CONCLUSION: Analysis of pooled data from the CRYSTAL and OPUS studies confirms the consistency of the benefit obtained across all efficacy end-points from adding cetuximab to first-line chemotherapy in patients with KRAS wild-type mCRC. BRAF mutation does not appear to be a predictive biomarker in this setting, but is a marker of poor prognosis.
AB - BACKGROUND: The CRYSTAL and OPUS randomised clinical trials demonstrated that adding cetuximab to first-line chemotherapy in patients with KRAS wild-type metastatic colorectal cancer (mCRC) significantly improved treatment outcome compared with chemotherapy alone. The objective of this pooled analysis was to further investigate these findings in patients with KRAS wild-type tumours using extended survival data and following an enhancement in the ascertainment rate of KRAS and BRAF tumour mutation status from these studies.METHODS: Pooled individual patient data from each study were analysed for overall survival (OS), progression-free survival (PFS) and best overall response rate (ORR) in patients evaluable for KRAS and BRAF mutation status. Treatment arms were compared according to mutation status using log-rank and Cochran-Mantel-Haenszel tests.RESULTS: In 845 patients with KRAS wild-type tumours adding cetuximab to chemotherapy led to a significant improvement in OS (hazard ratio [HR] 0.81; p=0.0062), PFS (HR 0.66; p<0.001) and ORR (odds ratio 2.16; p<0.0001). BRAF mutations were detected in 70/800 evaluable tumours. No significant differences were found in outcome between the treatment groups in these patients. Prognosis was worse in each treatment arm for patients with BRAF tumour mutations compared with those with BRAF wild-type tumours.CONCLUSION: Analysis of pooled data from the CRYSTAL and OPUS studies confirms the consistency of the benefit obtained across all efficacy end-points from adding cetuximab to first-line chemotherapy in patients with KRAS wild-type mCRC. BRAF mutation does not appear to be a predictive biomarker in this setting, but is a marker of poor prognosis.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Randomized Controlled Trials as Topic
KW - Treatment Outcome
KW - Europe
KW - Disease-Free Survival
KW - Neoplasm Metastasis
KW - Antibodies, Monoclonal/pharmacology
KW - Antineoplastic Agents/pharmacology
KW - Mutation
KW - Colorectal Neoplasms/drug therapy
KW - Genes, ras
KW - ras Proteins/metabolism
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Randomized Controlled Trials as Topic
KW - Treatment Outcome
KW - Europe
KW - Disease-Free Survival
KW - Neoplasm Metastasis
KW - Antibodies, Monoclonal/pharmacology
KW - Antineoplastic Agents/pharmacology
KW - Mutation
KW - Colorectal Neoplasms/drug therapy
KW - Genes, ras
KW - ras Proteins/metabolism
U2 - 10.1016/j.ejca.2012.02.057
DO - 10.1016/j.ejca.2012.02.057
M3 - SCORING: Journal article
C2 - 22446022
VL - 48
SP - 1466
EP - 1475
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
IS - 10
M1 - 10
ER -
