Neoadjuvant chemotherapy (NCT) plus targeted agents versus NCT alone in colorectal liver metastases patients: A systematic review and meta-analysis.

Chun-Hui Cui,Shu-Xin Huang,Zong-Hai Huang,Jin-Long Yu,Jia Qi,Hui-Juan Zhu

doi:10.18632/oncotarget.5875

Abstract

To assess the efficacy of neoadjuvant chemotherapy (NCT) plus targeted agents versus NCT alone for the treatment of colorectal liver metastases (CRLM) patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All clinical studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), hepatic resection and R0 hepatic resection rate were extracted and analyzed using Comprehensive MetaAnalysis software (Version 2.0). A total of 40 cohorts with 2099 CRLM patients were included: 962 patients were treated with NCT alone, 602 with NCT plus anti-epidermal growth-factor receptor (EGFR)-monoclonal antibodies (MoAbs) and 535 with NCT plus bevacizumab. Pooled ORR was significantly higher for NCT plus bevacizumab or anti-EGFR-MoAbs than NCT alone [relative risk (RR) 1.53, 95% CI 1.30-1.80; p < 0.001; RR 1.53, 95% CI: 1.27-1.83, p < 0.001; respectively]. NCT plus bevacizumab significantly improved R0 hepatic resection rate (RR 1.61, 95% CI: 1.27-2.04, p < 0.001), but not for overall hepatic resection rate (RR 1.26, 95% CI: 0.81-1.94, p = 0.30). While hepatic resection and R0 hepatic resection rate was comparable between NCT plus anti-EGFR-MoAbs and NCT alone (p = 0.42 and p = 0.37, respectively). In comparison with NCT alone, NCT plus bevacizumab significantly improve ORR and R0 hepatic resection rate but not for hepatic resection rate. Our findings support the need to compare NCT plus bevacizumab with NCT alone in the neoadjuvant setting in large prospective trials due to its higher hepatic resection rate and R0 hepatic resection rate in CRLM patients.

Highlights

Colorectal cancer (CRC) is one of the most common malignant tumors throughout the world with over 1.2 million new cases and 608700 deaths estimated to occur annually [1]
In comparison with neoadjuvant chemotherapy (NCT) alone, NCT plus bevacizumab or anti-epidermal growth-factor receptor (EGFR)-monoclonal antibodies (MoAbs) significantly improve objective response rate (ORR) (RR 1.53, 95% confidence interval (CI) 1.30–1.80; p < 0.001; relative risk (RR) 1.53, 95% CI: 1.27–1.83, p < 0.001; respectively), NCT plus bevacizumab significantly improved R0 hepatic resection rate in comparison with NCT alone
The trial conducted by Ye L.C et al showed that cetuximab combined with chemotherapy improved the resectability of liver metastases and improved response rates (57.1% versus 29.4%) and 3-year survival (41% versus 18%) in comparison with chemotherapy alone for K-RAS wild-type colorectal liver metastases (CRLM) patients [33], while the New EPOC trial showed that the addition of cetuximab to neoadjuvant chemotherapy for K-RAS wild-type CRLM patients resulted in shorter progression-free survival (HR 1.48, 95% CI: 1.04–2.12, p = 0.03) [29]

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignant tumors throughout the world with over 1.2 million new cases and 608700 deaths estimated to occur annually [1]. Half of CRC patients will develop colorectal liver metastases (CRLM) during the course of their disease, with 15% of patients having liver metastatic lesions at the time of diagnosis [2]. 70–80% of patients will relapse in two years after liver surgery, and about 80% of patients with colorectal liver metastases have unresectable disease at presentation [7]. When treating unresectable liver metastases of colorectal cancer, “conversion therapy” has been applied to reduce the tumor size and facilitate resection via preoperative chemotherapy [12, 13]. Neoadjuvant chemotherapy combined surgery for liver metastasis is regarded as an effective strategy in CRLM patients

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