Cetuximab/Irinotecan-Chemotherapy in KRAS Wild-type Pretreated Metastatic Colorectal Cancer: A Pooled Analysis and Review of Literature.

Introduction: Cetuximab and irinotecan are effective agents in advanced colorectal cancer (CRC) after either irinotecanor oxaliplatin-based first-line chemotherapy. Here, the efficacy of this combination in patients with the KRAS wild-type gene as second- or further-line therapy is reviewed and data are collected in a pooled analysis. Methods: Studies that enrolled pretreated CRC patients for second-line therapy or beyond were identified using electronic databases (PubMed and EMBASE). A systematic analysis was conducted using Comprehensive Meta Analysis (version 2.2.064) to calculate the event rate of response and the 95% confidence interval. The weighted median overall survival (OS) and progression-free survival (PFS) were also calculated with NCSS 2007 software. We tested for significant heterogeneity using Cochran’s chi-square test and the I² index. Results: Twenty-five studies published between 2007 and 2012 were eligible for this analysis, with a total of 1,712 KRAS wild-type patients enrolled. The overall response rate was 31.9% with similar response rates of 28.7% for second-line treatment and 31.1% for third or further lines. The overall weighted median OS and PFS were 12.5 and 6 months with a weighted OS of 11.56 and 12.2 months for second- and further-line CRC settings, respectively. Conclusion: In metastatic KRAS wild-type CRC patients pretreated with one or more lines of therapy, cetuximab plus irinotecan-based chemotherapy is an active treatment. Response rates and survival outcomes appear similar in second-line therapy or beyond.