Significance Of Cetuximab In The Conversion Therapy Of Patients With Colorectal Liver Metastases:A Meta-analysis

Objective: To evaluate the effect of adding cetuximab(Cet)to chemotherapy on the improvement of resection rate and survival benefit in initially unresectable patients with colorectal liver metastases(CRLM).Background : Colorectal cancer is currently the third most common cancer in the world,with the second highest mortality rate.About 20% of patients had metastatic lesions at the initial diagnosis,and the liver was the most common organ for hematogenous metastasis of colorectal cancer.For CRLMs,surgical resection after chemotherapy can significantly improve the survival benefit.However,there is no systematic evaluation conclusion on whether Cet can further improve the resection rate and improve the survival benefit in patients with RAS wild-type.Therefore,we carry out the meta-analysis to determine the significance of Cet on CRLMs.Methods: We retrieved articles from three famous databases,Pubmed,Embase and Cochrane Library,up to February 2019.The types of studies included were prospective studies,including randomized controlled trials(RCTs),non-RCTs,and single-arm studies.Main Outcome Measures: R0 resection rate,objective response rate(ORR),progressionfree survival(PFS),overall survival(OS).R0 resection rate and ORR were assessed by relative risk(RR),PFS and OS by hazard ratio(HR).Each of the ORR and R0 resection rate included in the studies was summarized for quantitative analysis.Data analysis was performed using stata15.0 software.Results: 12 clinical studies met inclusion criteria,of which 4 were single-arm studies and 8 were RCTs.No eligible non-RCTs were retrieved.The results showed that the addition of Cet to chemotherapy regimen in KRAS wild-type CRLMs significantly increased R0 resection rate(RR=2.03,95% confidence interval(CI): 1.25-3.29),ORR(RR= 1.76,95% CI: 1.40-2.21)and significantly improved survival benefit(PFS,OS)(HR=0.63,95% CI: 0.50-0.79;HR=0.74,95% CI : 0.55-0.99).In patients with RAS wild-type(both KRAS and NRAS are wild-type)CRLM,adding Cet to chemotherapy could further improve the R0 resection rate(RR=2.81,95% CI: 1.74-4.54),ORR(RR=2.19,95% CI: 1.76-2.74),and show more significant survival benefit(PFS,OS)(HR=0.43,95% CI: 0.34-0.53;HR=0.49,95% CI : 0.36-0.66).Among them,for KRAS wild-type patients,Cet combined with chemotherapy could increase the ORR up to 72% and make as many as 42 % of the initially unresectable patients received radical resection.The multidisciplinary team(MDT)group had higher conversion therapy rate(36% vs 26%)than the Cet group without MDT.Conclusions: For intitally unresectable CRLMs of RAS wild-type,adding Cet to chemotherapy can signiflancedly increase the resectable conversion rate and obtain higher survival benefit.