Abstract
614 Background: Surgery remains the standard of care for patients with colorectal liver metastases (CLM) with a 5-year survival rate approaching 35%. Nordlinger et al. demonstrated perioperative chemotherapy confers a survival benefit in selected patients with CLM. The use of targeted molecular therapy in combination with neoadjuvant chemotherapy in CLM, however, remains controversial. We reviewed the literature of combination neoadjuvant chemotherapy and targeted molecular therapy on resectable and initially unresectable CLM. Methods: A literature search of databases (Medline and PubMed) was conducted to identify studies on neoadjuvant chemotherapy plus targeted molecular therapy in the management of resectable or initially unresectable CLM. We calculated pooled odds ratio (OR) and 95% confidence intervals (CI) using a random effects model for the relationship of combination neoadjuvant treatment on overall response rate and resectability rate. The analysis was stratified according to study design. Results: Ten studies were analysed, which included 828 patients that underwent systemic chemotherapy and molecular targeted therapy for CLM. Seven studies utilized cetuximab and three utilized bevacizumab. The use of combination neoadjuvant therapy was associated with an overall response rate of 73% (95% CI: 68-78%) and no heterogeneity was observed in the studies (I2=0.00, p=0.77). R0 resection rate after combination neoadjuvant therapy was 56% (95% CI: 25-82%), however, high levels of heterogeneity was observed (I2=94.02, p<0.001). Overall median PFS was 13.7 months. Conclusions: Current evidence suggests that neoadjuvant chemotherapy in combination with molecular targeted agents in the treatment of CLM confers high overall response rates. Combination treatment may also significantly increase resectability rates in initially unresectable CLM. However these results have not translated into significant survival benefits. The role of targeted molecular therapy, with a focus on the molecular mechanism of action in the adjuvant versus metastatic settings, requires further research.
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