Efficacy and Safety of Everolimus Combined with Endocrine Therapy for Hormone Receptor-positive Advanced Breast Cancer: A Systematic Review
PENG Jia1,2, TAN Bo-yu1, KONG Xiao-min1,2, DENG Nan1*
1. Department of Pharmacy, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China; 2. Medical College,Hunan Normal University,Changsha 410006, China
Abstract��OBJECTIVE To systematically review the effect and safety of everolimus combined with endocrine therapy for hormone receptor-positive advanced breast cancer.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 and CNKI from the date of their establishment to March 2017. According to the inclusion criteria,assessed the quality for the requirements of RCT and Meta analysis were performed with Rev-Man 5.3 software.RESULTS Of 518 articles collected,a total of 7 RCTs involving 1 823 patients were included. The results of Meta-analyses showed that: 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��0.001),improve the clinical benefit rate(OR=2.31,95%CI:1.49~3.59,P=0.000 2), 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=1.22,95%CI:0.61-2.48,P=0.57). The most common adverse effects of everolimus combined with endocrine therapy are fatigue,stomatitis,anorexia,hot flashes,rash,diarrhea,pneumonia and hyperglycemia.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.
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PENG Jia, TAN Bo-yu, KONG Xiao-min, DENG Nan. Efficacy and Safety of Everolimus Combined with Endocrine Therapy for Hormone Receptor-positive Advanced Breast Cancer: A Systematic Review. Chinese Pharmaceutical Journal, 2018, 53(3): 228-233.
ME I. Recent research advances in breast cancer [EB/OL]. http://cancer.cmt.com.cn/detail/1290259.html.
[2]
CAI J Q,SUN H,WEI X X,et al. Influence of down-regulated long noncoding RNA H19 on invasion of tamoxifen-resistant breast cancer cell lines[J]. Chin Pharm J(�й�ҩѧ��־),2016,51(11):880-883.
[3]
BRUFSKY A M. Long-term management of patients with hormone receptor-positive metastatic breast cancer: concepts for sequential and combination endocrine-based therapies[J]. Cancer Treat Rev,2017,59(6):22-32.
[4]
HAMMOND M E,HAYES D F,DOWSETT M,et al. American society of clinical oncology /college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J]. J Clin Oncol,2010,28(16):2784-2795.
[5]
OSBORNE C K,SCHIFF R. Mechanisms of endocrine resistance in breast cancer[J]. Ann Rev Med,2011,62(1):233-247.
[6]
XU Y,SUN Q. Headway in resistance to endocrine therapy in breast cancer[J]. J Thorac Dis,2010,2(3):171-177.
[7]
BECK J T. Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor-positive advanced breast cancer[J]. Onco Targets Ther,2015,8(1):3629-3638.
[8]
BEAVER J A, PARK B H. The BOLERO-2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone receptor-positive advanced breast cancer[J]. Future Oncol,2012,8(6):651-657.
[9]
WOLFF A C, LAZAR A A, BONDARENKO I,et al. Randomized phase �� placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer[J]. J Clin Oncol,2013,31(2):195-202.
[10]
BACHELOT T, BOURGIER C, CROPET C, et al. Randomized phase �� trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive,human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a gineco study[J]. J Clin Oncol,2012,30(22):2718-2724.
[11]
BASELGA J, CAMPONE M, PICCART M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer[J]. Der Onkologe,2012,366(6):520-529.
[12]
BASELGA J, SEMIGLAZOV V, VAN D P,et al. Phase �� randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer[J]. J Clin Oncol,2009,27(16):2630-2637.
[13]
LIN P L, HAO Y, XIE J,et al. Real-world effectiveness of everolimus-based therapy versus endocrine monotherapy and chemotherapy in patients of HR+/HER2-breast cancer with liver metastasis in the USA[J]. Expert Opin Pharmacother,2015,16(14):2101-2111.
[14]
NOGUCHI S,MASUDA N,IWATA H,et al. Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative,hormone-receptor-positive breast cancer in BOLERO-2[J]. Breast Cancer,2014,21(6):703-714.
[15]
HAO Y, LIN P L, XIE J, et al. Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer[J]. J Comp Eff Res,2015,4(4):315-326.
[16]
GUO Y F,BIAN L,WANG T, et al. Efficacy analysis of everolimus combined endocrine therapy in treatment of heavily pretreated patients with HR positive advanced breast cancer[J]. Acad J Chin PLA Med Sch(��ž�ҽѧԺѧ��),2015,36(6):545-548.
[17]
HARE S H, HARVEY A J. mTOR function and therapeutic targeting in breast cancer[J]. Am J Cancer Res, 2017, 7(3):383-404.
[18]
BEAVER J A,PARK B H. The BOLERO-2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone r eceptor-positive advanced breast cancer[J]. Future Oncol,2012,8(6):651-657.
[19]
HADJI P, ASMAR L, NES J G H V,et al. The effect of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial: a Meta-analysis of the US,German,Netherlands,and Belgium sub-studies[J]. J Cancer Res Clin Oncol,2011,137(6):1015-1025.
[20]
PICCART M,HORTOBAGYI G N, CAMPONE M,et al. Everolimus plus exemestane for hormone-receptor-positive,human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2?[J]. Ann Oncol,2014,25(12):2357-2362.
2018, Vol. 53 
