Promising biomarkers for predicting the outcomes of patients with KRAS wild‐type metastatic colorectal cancer treated with anti‐epidermal growth factor receptor monoclonal antibodies: A systematic review with meta‐analysis. Issue 8 (13th July 2013)

• Record Type: Journal Article
• Authors: Yang, Zu‐Yao; Wu, Xin‐Yin; Huang, Ya‐Fang; Di, Meng‐Yang; Zheng, Da‐Yong; Chen, Jin‐Zhang; Ding, Hong; Mao, Chen; Tang, Jin‐Ling
• Is Part Of: International journal of cancer. Volume 133:Issue 8(2013:Oct. 15)
• Page Start: 1914
• Page End: 1925
• Publication Date: 2013-07-13
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28153
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>KRAS</italic> mutations have been established as a major predictive biomarker for resistance to the treatment of metastatic colorectal cancer (mCRC) with anti‐epidermal growth factor receptor monoclonal antibodies (anti‐EGFR MoAbs). However, many patients with <italic>KRAS</italic> wild‐type tumors still do not respond to the treatment. We conducted a systematic review with meta‐analysis to assess whether <italic>BRAF</italic> mutations, <italic>PIK3CA</italic> mutations and PTEN loss can predict the outcomes of patients with <italic>KRAS</italic> wild‐type mCRC treated with anti‐EGFR MoAbs. Studies that explored the association of one or more of the three biomarkers with progression‐free survival (PFS), overall survival (OS) and/or objective response rate (ORR) were identified through August 2012. Summary hazard ratios (HRs) and rate differences (RDs) and corresponding 95% confidence intervals (CIs) were calculated by using the random‐effects model. <italic>BRAF</italic> mutations, <italic>PIK3CA</italic> exon 20 mutations and PTEN loss were all associated with shorter PFS (HR = 2.59, 95% CI 1.67–4.03; HR = 2.52, 95% CI 1.33–4.78 and HR = 1.75, 95% CI 1.19–2.56, respectively), shorter OS (HR = 2.74, 95% CI 1.79–4.19; HR = 3.29, 95% CI 1.60–6.75 and HR = 1.85, 95% CI 1.30–2.64, respectively) and lower ORR (RD = −36%, 95% CI −44 to −28%; RD = −38%, 95% CI −51 to −24% and RD = −41%, 95% CI −68 to −14%, respectively). <italic>PIK3CA</italic> exon 9 mutations were associated with none of the outcomes. Studies with relevant data consistently demonstrated a stronger predictive power of combined multiple biomarkers as compared to one alteration alone. These results suggest that <italic>BRAF</italic> mutations, <italic>PIK3CA</italic> exon 20 mutations and PTEN loss are predictive of better outcomes in <italic>KRAS</italic> wild‐type mCRC treated with anti‐EGFR MoAbs. However, the quality of included studies varied, and some of the meta‐analyses were limited by significant between‐study heterogeneity. In the future, well‐designed large randomized controlled trials conducted in <italic>KRAS</italic> wild‐type mCRC patients with subgroup analysis according to <italic>BRAF</italic>, <italic>PIK3CA</italic> exon 20 and PTEN status are essential to fully assess the clinical relevance of these biomarkers.</p> </abstract>