Effects Of Anti-VEGF And Anti-EGFR Targeted Drugs Combined With Chemotherapy As First-line Therapy For Metastatic Colorectal Cancer: A Meta-analysis

Background: The incidence of colorectal cancer in the world is increasing year by year,and the incidence in China has risen faster than the international level.It ranks fourth in the common tumors,second only to the lung,stomach,liver cancer,and it has become a common malignant tumor.Colorectal cancer is occult,and many patients have distant metastasis when they are diagnosed.The traditional surgery combined with chemotherapy can only get limited survival benefit,and the emergence of targeted drugs prolong survival of tumor patients.With the development of targeted drugs,targeting tumor cells,effective control of tumor development and reduction of adverse reactions to other normal organs are the focus of clinical research.Currently,both anti-EGFR monoclonal antibodies and anti-VEGF monoclonal antibodies have been approved for metastatic colorectal cancer.But for specific dominant population,there is no uniform treatment.The effects of side effects on the quality of life should be included in the overall treatment strategy.Therefore,it is an urgent problem that how to select target drug better.Objective: The NCCN guidelines recommend anti-VEGF or anti-EGFR as a standard regimen for first-line treatment of RAS wild metastatic colorectal cancer(m CRC).However,there is no systematic evaluation of the difference between the prognosis of anti-VEGF and anti-EGFR targeting drugs in metastatic colorectal cancer.Therefore,the effect of chemotherapy combined with anti-EGFR and anti-VEGF targeting drugs on metastatic colorectal cancer is to be systematically evaluated.Methods: While tracing references we used computer to search Cochrane,Pubmed,Web,of,science,Embase,ASCO,Trials,ESMO,Clinical,Chinese biomedical literature database,etc.Head-to-head randomized controlled trials(RCTs)of anti-VEGF combined with chemotherapy versus anti-EGFR combined with chemotherapy in the treatment of metastatic colorectal cancer(m CRC)were collected,and it was evaluated according to the Cochrane system evaluation manual,5.3 quality evaluation criteria.Stata 12.0 software and Revman5.3 were used for meta-analysis.Results: A total of 3 clinical randomized controlled trials were enrolled,with a total of 2014 subjects.The results of meta-analysis showed that a given anti-EGFR or anti-VEGF targeted drugs combined with chemotherapy in patients with m CRC,regardless of the wild-type KRAS[HR=1.03,95%CI:0.93~1.13,P>0.05] or RAS [HR=0.92,95%CI:0.71~1.18,P>0.05],progression free survival(PFS)were not statistically significant.As for overall survival(OS)that first treated with anti-EGFR combined with chemotherapy regimen,the KRAS wild-type patients [HR=0.82,95%CI:0.72~0.93,P?0.01] and RAS wild-type patients[HR=0.79,95%CI:0.67 ~ 0.93,P ? 0.01] were better than that of anti-VEGF combined with chemotherapy;The objective remission rates(ORR)were significantly increased in KRAS wild-type patients after receiving anti-EGFR combined with chemotherapy [RR=0.84,95%CI:0.76~0.94,P?0.01].The improvement of ORR in RAS wild-type patients is superior to that in KRAS wild-type patients [RR=0.80,95%CI:0.68 ~ 0.93,P ? 0.01];Whether anti-EGFR or anti-VEGF targeting drugs combined with chemotherapy,the left colon cancer patients had a better survival benefit PFS [HR=0.64,95%CI:0.45~0.91,P?0.01] and OS[HR=0.53,95%CI:0.36~0.76,P?0.01] than the right half colon cancer.In the anti-EGFR group,the efficacy evaluation indexes,such as the early tumor shrink(ETS)[RR=0.64,95%CI:0.51~0.79,p?0.01],and the deepness of response(Dp R)[RR=0.72,95%CI:0.62~0.84,p?0.01],were better than those of the anti-VEGF group.There was no significant difference in blood toxicity and diarrhea between anti-EGFR group and anti-VEGF group [RR=0.98,95%CI:0.92~1.03,p>0.05];Above three-level rash in anti-EGFR group [RR=0.79,95%CI:0.76~0.82,p?0.01];Above three-level hypertension in anti-VEGF group [RR=1.05,95%CI:1.03~1.07,p?0.01].Conclusion:(1)In KRAS or RAS wild-type m CRC patients,anti-EGFR monoclonal antibody may be the first choice for first-line treatment of m CRC,especially in left colon cancer.(2)In terms of the location of the tumor,patients with left colon cancer have a better survival advantage than the right colon cancer,regardless of the targeting drugs they received.(3)Anti-EGFR combined with FOLFOX or FOLFIRI improve ORR?ETS and Dp R of metastatic colorectal cancer.(4)In terms of security,anti-EGFR targeting drugs increased the risk of 3-4 level rash,while anti-VEGF increased the risk of 3-4 level hypertension in the process of treatment.