Loss of PTEN expression as a predictor of resistance to anti-EGFR monoclonal therapy in metastatic colorectal cancer: evidence from retrospective studies

Abstract

To investigate the predictive value of loss of PTEN expression in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR monoclonal therapy. Studies were systematically identified to investigate the relationship between PTEN expression and clinical outcome in mCRC patients treated with anti-EGFR MoAbs. Clinical outcomes included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated using a fixed-effects model or a random-effects model according to the heterogeneity between the studies. A total of 852 patients were included in the final meta-analysis. The rate of loss of PTEN expression was 28.4% (242/852). The overall pooled RR for ORR was 0.413 (95% confidence intervals (CI), 0.177-0.965) when patients with loss of PTEN expression were compared with those with normal PTEN expression. Anti-EGFR monoclonal therapy resulted in improved PFS (HR, 0.466; 95% CI, 0.292-0.640) and OS (HR, 0.689 [95% CI, 0.482-0.896]) in patients unselected by KRAS mutation with normal PTEN expression over loss of PTEN expression. A better prognosis, as reflected by PFS (HR, 0.344; 95% CI, 0.154-0.533) and OS (HR, 0.544; 95% CI, 0.285-0.803), was observed in wild-type KRAS patients with normal PTEN expression versus loss of expression. Loss of expression of PTEN is a potential biomarker for resistance to anti-EGFR monoclonal therapy, particularly in mCRC patients with KRAS wild type.