Anti-epidermal growth factor receptor monoclonal antibody-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of PIK3CA mutations in KRAS wild-type patients

INTRODUCTION We conducted a meta-analysis to dissect the association between PIK3CA mutations (exon 9 and exon 20) and resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in KRAS wild-type metastatic colorectal cancer (mCRC) patients. MATERIAL AND METHODS In 11 previously published studies, 864 cancer patients were treated with cetuximab or panitumumab-based therapy. Primary outcomes included objective response (complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). We calculated the odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CIs) to estimate the risk or hazard. We found consistent and clinically substantial risk or hazard for objective response, PFS, and OS in the cetuximab or panitumumab-treated mCRC patients. RESULTS PIK3CA mutations as a whole were associated with reduced response and poor PFS and OS in KRAS wild-type mCRC patients (objective response: OR = 0.42 and 95% CI 0.23-0.75; PFS: HR = 1.54 and 95% CI 1.13-2.09; and OS: HR = 1.4 and 95% CI 1.02-1.91). PIK3CA exon 9 mutations had no effect, whereas exon 20 mutations were associated with a worse outcome compared with wild types, with an OR of 0.21 (95% CI 0.05-0.93). CONCLUSIONS PIK3CA mutations as a whole might be useful prognostic factors for assessing clinical outcomes of anti-EGFR MoAb-based chemotherapies in KRAS wild-type mCRC patients. In particular, PIK3CA exon 20 mutations were significantly associated with lack of response.