The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials

• Published in: European journal of cancer (1990) Vol. 70; pp. 87 - 98
• Main Authors: Holch, Julian Walter, Ricard, Ingrid, Stintzing, Sebastian, Modest, Dominik Paul, Heinemann, Volker
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2017; Elsevier Science Ltd
• Subjects: Angiogenesis Inhibitors - therapeutic use; Anti-EGFR; Anti-VEGF; Antibodies, Monoclonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biomarkers; Cancer; Cetuximab; Chemotherapy; Clinical trials; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Confidence intervals; Epidermal growth factor receptors; Hematology, Oncology and Palliative Medicine; Humans; Medical research; Meta-analysis; Metastases; Metastatic colorectal cancer; Monoclonal antibodies; Panitumumab; Patients; Pharmacology; Predictive biomarker; Primary tumour location; Prognosis; Prognostic biomarker; Randomized Controlled Trials as Topic; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Retrospective Studies; Sidedness; Subgroups; Survival; Survival Analysis; Targeted cancer therapy; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Anti-EGFR; Panitumumab; Primary tumour location; Anti-VEGF; Sidedness; Cetuximab; Metastatic colorectal cancer; Predictive biomarker; Prognostic biomarker; Bevacizumab
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2016.10.007

Abstract Background Retrospective subgroup analyses suggest that primary tumour location (PTL) has a prognostic importance and relates to response to targeted therapy. Methods We conducted a meta-analysis of first-line clinical trials available up to October 2016, which assessed the relevance of PTL in patients with metastatic colorectal cancer (mCRC). Right- and left-sided colorectal cancers were differentiated (RC and LC). Results In 13 first-line randomised controlled trials and one prospective pharmacogenetic study, RC was associated with a significantly worse prognosis compared with LC (hazard ratio [HR] for overall survival: 1.56; 95% confidence interval [CI]: 1.43–1.70; P < 0.0001). A meta-analysis of PRIME and CRYSTAL study suggests that PTL was predictive of survival benefit from addition of anti-EGFR antibody to standard chemotherapy in patients with RAS wild-type tumour (overall survival, HR for LC: 0.69; 95% CI: 0.58–0.83; P < 0.0001 and HR for RC: 0.96; 95% CI: 0.68–1.35; P = 0.802). A meta-analysis of FIRE-3/AIO KRK0306, CALGB/SWOG 80405 and PEAK study indicates that patients with RAS wild-type LC had a significantly greater survival benefit from anti-EGFR treatment compared with anti-VEGF treatment when added to standard chemotherapy (HR 0.71; 95% CI: 0.58–0.85; P = 0.0003). By contrast, in patients with RC, benefit from standard therapy was poor and bevacizumab-based treatment was numerically associated with longer survival (HR 1.3; 95% CI: 0.97–1.74; P = 0.081). Conclusions The present meta-analysis demonstrates that PTL is prognostic in mCRC. Further, it supports the conclusion that patients with left-sided RAS wild-type mCRC should be preferentially treated with an anti-EGFR antibody. In right-sided mCRC, chemotherapy plus bevacizumab is a treatment option, but optimal treatment has yet to be defined.