Fulvestrant plus targeted agents versus fulvestrant alone for treatment of hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy: a meta-analysis of randomized controlled trials.
To compare the addition of targeted agents to fulvestrant with fulvestrant alone in hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy; a meta-analysis of all relevant randomized controlled trials was performed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and June 2016. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed. Eight trials with a total of 2,470 patients were included in this meta-analysis. Compared with fulvestrant alone, combination therapy improved PFS (HR = 0.79; 95% CI 0.72-0.87; P = 0.00), increased ORR (RR = 1.70; 95% CI 1.30-2.21; P = 0.00), and showed a trend of increase in DCR (RR = 1.27; 95% CI 0.96-1.69, P = 0.09). In network analysis, only CD4/6 and PI3K/m-TOR inhibitors showed significant treatment effects with a P-score of 0.9999 and 0.7615, respectively. Patients treated with combination therapy developed more grade 3 or greater toxic effects (RR = 1.24; 95% CI 1.13-1.36; P = 0.00). Combining targeted agents with fulvestrant showed benefit but with increased toxicity in patients with advanced breast cancer compared with fulvestrant alone. Biomarkers for treatment optimization are lacking. The CD4/6 and PI3K/m-TOR pathways merit further investigation.
Department of Medical Oncology, Shantou Central Hospital, Shantou, Guangdong, China.
Wen-Zhao
WZ
Lin
Department of Respiratory Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Qi-Ni
QN
Xu
Department of Respiratory Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Hong-Biao
HB
Wang
Department of Medical Oncology, Shantou Central Hospital, Shantou, Guangdong, China. lxuyuan@qq.com.
Xu-Yuan
XY
Li
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000378:metabolism; D016896:Treatment Outcome
D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol
Breast cancer; Fulvestrant; Meta-analysis; Targeted therapy