Use of early tumor shrinkage to predict long-term outcome in metastatic colorectal cancer treated with cetuximab

Early tumor shrinkage (ETS) is associated with long-term outcome in patients with chemorefractory metastatic colorectal cancer (mCRC) receiving cetuximab. This association was investigated in the first-line setting in the randomized CRYSTAL and OPUS mCRC trials, after controlling for KRAS tumor muta...

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Bibliographic Details
Published in:Journal of clinical oncology Vol. 31; no. 30; p. 3764
Main Authors: Piessevaux, Hubert, Buyse, Marc, Schlichting, Michael, Van Cutsem, Eric, Bokemeyer, Carsten, Heeger, Steffen, Tejpar, Sabine
Format: Journal Article
Language:English
Published: United States 20.10.2013
Subjects:
Adult
Aged
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Cetuximab
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
Disease-Free Survival
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Staging
Predictive Value of Tests
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins p21(ras)
ras Proteins - genetics
ROC Curve
Sensitivity and Specificity
Time Factors
Treatment Outcome
ISSN:1527-7755, 1527-7755
Online Access:Get more information
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Summary:Early tumor shrinkage (ETS) is associated with long-term outcome in patients with chemorefractory metastatic colorectal cancer (mCRC) receiving cetuximab. This association was investigated in the first-line setting in the randomized CRYSTAL and OPUS mCRC trials, after controlling for KRAS tumor mutation status. Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. Time-dependent receiver operating characteristics provided Cτ-indices (time-dependent c-index). Cox regression models and subpopulation treatment effect pattern plot analysis investigated associations between ETS (radiologic tumor size decrease at week 8) and survival and progression-free survival (PFS). In both trials, in patients with KRAS wild-type mCRC, Cτ values for PFS and survival were higher (P < .001) in those receiving chemotherapy plus cetuximab versus chemotherapy alone, indicating a stronger predictive value of ETS for long-term outcome in these patients. In the CRYSTAL and OPUS trials, respectively, the cutoff value of ETS ≥ 20% (v < 20%) identified patients with KRAS wild-type mCRC receiving chemotherapy plus cetuximab with longer PFS (medians 14.1 v 7.3 months, hazard ratio [HR] = 0.32; P < .001, and medians 11.9 v 5.7 months, HR = 0.22; P < .001) and survival (medians 30.0 v 18.6 months, HR = 0.53; P < .001 and medians 26.0 v 15.7 months, HR = 0.43; P = .006). ETS was significantly associated with long-term outcome in patients with KRAS wild-type mCRC treated first-line with chemotherapy plus cetuximab. Validation in prospective trials is required to assess the value of this on-treatment marker in the clinical decision-making process.
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ISSN:1527-7755
1527-7755
DOI:10.1200/JCO.2012.42.8532