Efficacy And Safety Of Everolimus Combined With Endocrine Therapy For Hormone Receptor-positive Advanced Breast Cancer:A Systematic Review

Objective:To systematically review the effecy and safety of everolimus combined with endocrine therapy for hormone receptor-positive advanced breast cancer with the methods of systematic review and GRADE,and providing evidence for clinical practice and doctor make decisions.Methods:The randomized controlled trails(RCTs)on everolimus combined with endocrine therapy or everolimus in the treatment of endocrine failure were searched in PubMed,MEDLINE,CENTRAL,EMBASE,the Cochrane Library,China National Knowledge Infrastructrue(CNKI),Chinese Science and Technology Periodical Database(CMB),VIP,Wanfang Database from the date of their establishment to March 2018.No restrictions on language and publication status.The clinical trial registration platform and relevant journals were also manually searched up to March 2018.Two reviewers selected studies and extracted data independently according to pre-designed criteria,and unified data after cross-checking.According to the inclusion criteria,assessed the quality for the requirements of RCT and Meta analysis were performed with Rev-Man 5.3 software,graded the quality of evidence by GRADE,and made the conclusions as well as the recommendations.Results:Of 518 articles collected,a total of 7 RCTs involving 1823 patients were included.The results of meta-analyses showed that:In the hormone receptor-positive advanced breast cancer,compared with endocrine therapy alone,everolimus combined with endocrine therapy could prolong the progression-free survival(PFS)for patients with HR+ breast cancer(HR=0.53,95%CI:0.45?0.62,P<0.00001),improve the Clinical benefit rate(OR=2.31,95%CI:1.49?3.59,P=0.0002),improve the quality of life(HR=0.75,95%CI:0.60?0.94,P=0.01),but it could not improve objective response rate(OR=2.88,95%CI:0.93?8,92,P=0.07).The most common adverse effects of everolimus combined with endocrine therapy are fatigue,stomatitis,anorexia,hot flashes,rash,diarrhea,pneumonia and hyperglycemia.In the grades 3 to 4 adverse effects,compared with the control group,the combination of everolimus and endocrine therapy appeared stomatitis,diarrhea,hyperglycemia increasingly,and there was a significant difference between the two groups.The quality of evidence was morderate.Conclusion:The curative effect of everolimus combined with endocrine therapy is significantly better than endocrine therapy alone in hormone-positive breast cancer with adverse effects increased.Due to the limited quantity and quality of the included studies,more high quality RCTs with large sample size are needed to verify the above conclusion.