Evaluation Of The Efficacy And Safety Of PARP Inhibitors In The Treatment Of Recurrent Ovarian Cancer

Objective:In this paper,the existing research results were analyzed by using traditional Meta and network Meta-analysis methods to investigate the efficacy and safety of Polyadenosine diphosphate ribose polymerase inhibitors in the treatment of recurrent ovarian cance,hopeing to provide a reference for the clinical treatment of recurrent ovarian cancer.Methods:Two researchers independently searched Pubmed,EMBASE,Cochrane Library,China Journal Full-text Database(CNKI),VIP Chinese Science and Technology Journal Full-text Database(VIP),Wanfang Digital Journal Full-text Database,and China Biomedical Literature Database(CBM).Randomized controlled trails(RCTs)associated with PARP inhibitors(PARPis)for the treatment of recurrent OC were included.The data of the included documents were processed and analyzed by using Review Manager 5.3,Stata14.0 and Win BUGS 1.4 software.Results:A total of 9 articles were included in the study,including 2098 patients.This study separately conducted a traditional Meta-analysis of effectiveness and safety and a network meta-analysis of serious adverse reactions.1.Results of traditional Meta-analysisPARPis were more effective than placebo in all OC patients,BRCAmt patients and BRCAwt patients.In the total adverse reaction analysis,PARPis were more likely to cause total serious adverse reactions than placebo.PARPis combined with CHE were more likely to cause total serious adverse reactions than CHE alone.In each subgroup analysis of adverse reactions,PARPis were more likely to cause various serious adverse reactions than placebo.PARPis combined with CHE were more likely to cause severe anemia than CHE alone.2.Results of network meta-analysisThe results of PARPis in the treatment of OC lead to serious adverse reactions.For total serious adverse reactions,all of the investigated PARPis caused greater risk than placebo.The probability ranking of the four interventions were olaparib 400 mgbid < olaparib 300 mgbid < rucaparib 600 mgbid < niraparib 300 mgbid.For severe nausea,the results of the probability ranking were niraparib 300 mgbid < olaparib 300 mgbid < rucaparib 600 mgbid < olaparib 400 mgbid.For severe fatigue,niraparib 300 mgbid caused greater risk than placebo.The probability ranking of the four interventions were olaparib 300 mgbid < olaparib 400 mgbid < rucaparib 600 mgbid < niraparib 300 mgbid.For severe vomiting,niraparib 300 mgbid may have a greater risk than placebo.The probability ranking of the four interventions were rucaparib 600 mgbid < olaparib 300 mgbid < olaparib 400 mgbid < niraparib 300 mgbid.For severe anemia,niraparib 300 mgbid was more likely to cause anemia than placebo.The probability ranking of the four interventions were olaparib 300 mgbid < olaparib 400 mgbid < rucaparib 600 mgbid < niraparib 300 mgbid.For severe neutropenia,niraparib 300 mgbid,rucaparib 300 mgbid may have a greater risk compared with placebo.The probability ranking of the four interventions were olaparib 300 mgbid < olaparib 400 mgbid < rucaparib 600 mgbid < niraparib 300 mgbid.The results of serious adverse reactions caused by PARPis combined with CHE and CHE alone.For total serious adverse reactions,veliparib 60 mgqd combined with CHE compared with CHE may lead to a greater risk.The results of the probability ranking were CHE < olaparib 200 mgbid + CHE < veliparib 60 mgqd + CHE.For severe nausea,the probability ranking of the five interventions were olaparib 400 mgbid < CHE < veliparib 60 mgqd + CHE < olaparib 200 mgbid + CHE < olaparib 200 mgbid.For severe fatigue,the results of the probability ranking were olaparib 200 mgbid < CHE < veliparib 60 mgqd + CHE < olaparib 400 mgbid < olaparib 200 mgbid + CHE.For severe vomiting,the results of the probability ranking were: olaparib 200 mgbid < olaparib 200 mgbid + CHE < olaparib 400 mgbid < veliparib 60 mgqd + CHE < CHE.For severe anemia,olaparib 200 mgbid combined with CHE was more risky for severe anemia than CHE alone.The results of the probability ranking were CHE < olaparib 400 mgbid < veliparib 60 mgqd + CHE < olaparib 200 mgbid < olaparib 200 mgbid + CHE.For severe neutropenia,the probability ranking of the three interventions were CHE < olaparib 200 mgbid + CHE < veliparib 60 mgqd + CHE.Conclusion:1.Regardless of whether patients with recurrent ovarian cancer have BRCA mt,PARPis provide effective treatment,especially for patients with BRCA mt.2.Olaparib 300 mgbid may be a relatively less toxic drug in PARPis for the treatment of recurrent ovarian cancer.3.Rucaparib 600 mgbid treatment with OC has the least probability of causing severe vomiting,which may be a less gastrointestinal toxic drug in PARPis.4.Niraparib 300 mgbid.has the highest probability of causing severe anemia and neutropenia,which may be the most prone to cause hematological toxicity in PARPis.5.PARPis combined with chemotherapy may be more likely to cause serious adverse reactions than PARPis alone or chemotherapy alone.