A Systematic Review Of The Efficacy And Safety Of Pemetrexed/Platinum Chemotherapy Alone Or Combination With Gefitinib In The First-line Treatment Of Advanced Non-squamous NSCLC

Objective:Systematically evaluate the differences between gefitinib combined with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone of efficacy and safety in the first-line treatment of advanced non-squamous non-small cell lung(NSCLC)cancer.Methods:A systematic search of Ovid,PubMed,Nature e-news,Elton B Stephens Company(EBSCO),Nature Oncogene,Web of Science,China National Knowledge Infrastructure(CNKI)and China Biology Medicine disc and Web Platform Website were performed from January 2008 to January 2018.We searched the data about clinical controlled trial(CCT)of pemetrexed/platinum chemotherapy combined with gefitinib versus pemetrexed/platinum chemotherapy alone in initial treatment of advanced non-squamous NSCLC,and then we used RevMan5.0 to perform metaanalysis of these data.Results:This study performed a meta-analysis of 468 cases in a total of 7 clinical controlled trial(CCT),which mainly evaluate the differences between pemetrexed/platinum chemotherapy together with gefitinib and pemetrexed/platinum chemotherapy alone in terms of efficacy and safety in initial treatment of advanced non-squamous NSCLC.The efficacy indicators includes overall response rate(ORR),disease control rate(DCR)and 12-month survival rate.Comparing pemetrexed/platinum chemotherapy together with gefitini to chemotherapy alone for advanced non-squamous NSCLC patients,the pooled odds ratios(OR)of ORR was3.54,(95% confidential index(CI)= 1.52-8.24,P=0.004;Fig.2.1),the pooled OR of DCR was 3.47,(95% CI,1.68-7.15,P=0.0007;Fig.2.2),the pooled OR 12-month survival rate was 1.79,(95% CI,1.07-3.00,P=0.03;Fig.2.3).At the same time,the pooled OR of ORR which EGFR mutations was 6.89,(95% CI(3.64-13.06),P<0.00001;Fig2.1.1)and the pooled OR of ORR which EGFR mutations not checked was 2.40,(95% CI(1.08-5.36),P=0.03;Fig.2.1.1).The observed index of safety analysis includes the incidences of rash,diarrhea,nausea and vomiting,anemia,neutropenia and abnormal aminotransferases.Among these,the incidences relative risk(RR)of rash rate was 3.80,(P<0.00001;Fig.3.1),the incidences RR of diarrhea rate was 2.35,(P<0.0001;Fig.3.2),the incidences RR of nausea and vominting rate was 1.03,(P=0.82;Fig.3.3),the incidences RR of anemia rate was 1.08,(P=0.56;Fig.3.4),the incidences RR of neutropenia rate was 1.10,(P=0.43;Fig.3.5),the incidences RR of abnormal aminotransferases rate was 1.40,(P=0.06;Fig.3.6).Expect for the incidences RR of rash and diarrhea rate,the other four incidences(P>0.05)were not statistically significant.The incidence of rash and diarrhea in chemotherapy together with gefitinib was higher than that chemotherapy alone.When we consider these two side effects were all common adverse reactions to gefitinib,we carefully observed that the toxicities of the included studies were mainly grades I and II,and side effects greater than grade III suggested similar or fewer toxicities in the included studies.Conclusion:1.In aspects of efficacy,the total effective rate,disease control rate,and12-month survival rate of pemetrexed/platinum together with gefitinib in the first-line treatment of advanced non-squamous NSCLC.It was better than chemotherapy alone,especially for patients with EGFR mutations.2.In aspects of safety,combination drugs versus chemotherapy alone mainly reflected the side effects of gefitinib on skin rashes and diarrhea.Most of these side effect can be well controlled clinically.