| Purpose:To assess the efficacy and safety of EGFR-inhibitor (EGFRI) of based therapy versus non-EGFR-inhibitor therapy in advanced or metastatic colorectal cancer.Methods:literature resource:Cochrane Library,Medline,Embase,American Society of Clinical Oncology(ASCO).Inclusion criteria: (1) participating patients with metastatic (or advanced) colorectal cancer; (2) studying combined basic therapy(chemotherapy and best support care) with EGFR-inhibitor versus without EGFR-inhibitor and not confounding by additional agents or interventions; (3) randomized controlled trial; (4) phase II or III clinical trail.Analystic methods: subgroup analysis were made according to"combine with VEGF-inhibitor or not","difference of agent"and"status of the KRAS gene". Software Stata version 9.0 was use to heterogeneity test, sensitivity analysis, the efficacy analysis and the safty analysis. The efficacy including progression-free survival (PFS), median overall survival (OS), overall response rate (ORR). The safty data are adverse events (AEs), specific grade 3-4 toxicity data.Result:A Total of 9 literatures (10 randomized clinical trials and 5849 patients) were including in this analysis, 2926 patients in treatment group with EGFR-inhibitors and 2923 one in controlled group. There was heterogeneity in the initial result of PFS, OS and ORR. We eliminated the heterogeneity with subgroup analaysis. In the subgroup analysis, without the combination of bevacizumab, patients in EGFRI group resulted in a statistically significant improvement in PFS (Hazard Ratio:0.711, 95% confidence interval: 0.602-0.840)and ORR (Odd Ration: 2.378, 95%CI: 1.060-5.334) compared with non-EGFRI group. When combine with the bevacizumab, The addition of cetuximab to chemical therapy resulted in significantly shorter progression-free survival (HR: 1.238, 95%CI: 1.101-1.393) and objective respone rate(OR: 1.025, 95% CI: 0.852-1.235 ). No difference in OS between those two subgroups. However, when combined with non-bavcizumab therapy, The PFS was showing a statistically significant difference in favor of the cetuximab group(HR=0.710, 95%CI: 0.649-0.777), corresponding to an increase in odds of response for the addition of cetuximab therapy ( OR=1.766 , 95%CI: 1.058-2.947). PFS, OS and ORR of panitumumab have no difference in statistic(sPFS:HR0.927,95%CI:0.498-1.727;OS:1.217,95%CI:0.917-1.614;ORR:1.531,95%CI:0.440-5.325). Only one statistic description was made in gifitinib. Mutation of KRAS can decrease PFS(HR=1.398,95%CI: 1.145-1.708) and ORR with additonal EGFRI, compared to the controlled group of same gene type. Wild type patients treat with EGFRI, PFS can not be improved in statistics(HR=1.398,95%CI: 0.739-1.520),but ORR is higher than contolled group(OR =1.705,95CI:1.221-2.382). Compared with the controlled group, these 3/4 grade adverse events in treatment group got higher incidence rate: total 3/4 grade toxicity (72.17% vs 56.84%, OR=2.194, 95%CI:1.779-2.706) , 3/4 grade EGFRI-relative skin toxicity (23.78% vs 3.53%, OR=35.827, 95%CI:4.230-303.415), 3/4 grade diarrhea (20.60% vs 12.03%,OR=1.932, 95%CI: 1.484-2.516)), 3/4 grade fatigue (12.56% vs 9.19%,OR= 1.442 , 95%CI: 1.150-1.810), 3/4 grade injection sensitivity response (4.95% vs 2.13%,OR=2.169, 95%CI:1.246-3.776), Hypomagnesemia (29.02% vs 4.06% ,OR=12.288, 95%CI: 8.600-17.557). Conclusion:Combined with VEGF-inhibiter, addition of EGFRI did not get the better therapeutic efficacy than single agent, so we do not recommend to use the combination of"Cituximab/Panitumub+Bevacizumab+chemotherapy"in the mCRC patients. The addition of Cituximub can improve the PFS and ORR in mCRC patients without bevacizumab. MCRC patients who carried mutation KRAS gene type is inaptitude in EGFRI. Relative skin toxicity is the most common adverse event , but patients tolerated and can be controlled. Hypomagnesemia and sensitivity response should be taken caution in the course of EGFRI therapy.
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