Effect of first-line endocrine therapy in patients with hormone-sensitive advanced breast cancer: a network meta-analysis

Tingting Zhang,1 Fubin Feng,2 Wenge Zhao,3 Jinhui Tian,4 Yan Yao,3 Chao Zhou,2 Shengjie Dong,5 Congcong Wang,6 Chuanxin Zang,1 Qingliang Lv,7 Changgang Sun2,8 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, WeiFang, China; 2Department of Oncology, Weifang Traditional Chinese Hospital, WeiFang, China; 3Department of Oncology, Clinical Medical Colleges, Weifang Medical University, WeiFang, China; 4Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; 5Department of the Joint and Bone Surgery, Yantaishan Hospital, Yantai, China; 6Department of Oncology, Zibo Maternal and Child Health Hospital, Zibo, China; 7Department of Radiology, Weifang people’s Hospital, WeiFang, China; 8Department of Oncology, Affiliated Hospital of Weifang Medical University, WeiFang, China Background: Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis. Materials and methods: We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib. The results were presented with pooled odds ratio or hazard ratio (HR), and 95% credible interval (CrI). The primary outcomes were objective response rate (ORR) and progression-free survival/time to progression. Results: A total of 16 eligible articles (14 RCTs) involving 6,602 patients treated with 10 different first-line endocrine therapies were assessed in our network meta-analysis. Palbociclib plus letrozole was superior to anastrozole, letrozole, exemestane, fulvestrant 500 mg, and anastrozole plus fulvestrant (loading dose) (HR=0.44, 95% CrI: 0.33–0.58; HR=0.56, 95% CrI: 0.45–0.68; HR=0.45, 95% CrI: 0.32–0.61; HR=0.58, 95% CrI: 0.42–0.81; HR=0.50, 95% CrI: 0.37–0.68; respectively). However, there is no significant advantage compared with ribociclib plus letrozole (HR=1.00, 95% CrI: 0.72–1.39). In terms of ORR, ribociclib plus letrozole is more effective than palbociclib plus letrozole (odds ratio=1.30, 95% CrI: 0.83–2.02). Conclusion: Palbociclib plus letrozole and ribociclib plus letrozole might be the optimal first-line endocrine therapeutic choices for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer due to a longer progression-free survival/time to progression and a more efficacious ORR. Keywords: first-line endocrine therapy, progression-free survival, objective response rate, advanced breast cancer, network meta-analysis, randomized controlled tria