Comparative efficacy of different targeted therapies plus fulvestrant for advanced breast cancer following progression on prior endocrine therapy: a network meta-analysis

Tingting Zhang,1,* Fubin Feng,2,* Wenge Zhao,3 Yan Yao,3 Jinhui Tian,4 Chao Zhou,2 Chuanxin Zang,1 Cun Liu,1 Xue Wang,5 Changgang Sun2,6 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong, People’s Republic of China; 3Clinical Medical College, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 4Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 5Medical Colleges, Qingdao University, Qingdao, Shandong, People’s Republic of China; 6Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China *These authors contributed equally to this work Background: We performed a network meta-analysis of randomized controlled trials (RCTs) to indirectly compare the efficacy of different targeted agents with fulvestrant for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor type 2-negative (HER2–) advanced breast cancer (ABC) following progression on prior endocrine therapy.Methods: The titles/abstracts were searched from the PubMed, EMBASE, and the Cochrane Library databases for RCTs to evaluate the efficacy of palbociclib plus fulvestrant vs alternative targeted therapies plus fulvestrant for postmenopausal HR+/HER2– ABC following progression on prior endocrine therapy. In addition, the primary measured outcome was progression-free survival (PFS) and objective response rate. The surface under the cumulative ranking (SUCRA) value of each treatment was calculated to achieve the best ranking for each treatment.Results: A total of 11 studies, including 4,178 patients in the network meta-analysis, were included and analyzed. In terms of the pooled hazard ratios (HRs) for PFS, palbociclib plus fulvestrant was superior to other target agents plus fulvestrant (HR=0.62, 95% credible interval [CrI]: 0.40–0.96; HR=0.62, 95% CrI: 0.47–0.96; for pictilisib plus fulvestrant and buparlisib plus fulvestrant, respectively). Ribociclib plus fulvestrant has no difference in abemaciclib plus fulvestrant and palbociclib plus fulvestrant (HR =1.02, 95% CrI =0.72–1.45; HR =1.22, 95% CrI =0.84–1.78). In terms of objective response rate, compared with placebo plus fulvestrant, abemaciclib plus fulvestrant, dovitinib plus fulvestrant, buparlisib plus fulvestrant, and palbociclib plus fulvestrant had a significant difference (odds ratio [OR] =2.84, 95% CrI =1.91– 4.31; OR =3.62, 95% CrI =1.21–12.48; OR =1.80, 95% CrI =1.25–2.60; and OR =2.52, 95% CrI =1.43– 4.72, respectively).Conclusion: According to the present study, palbociclib plus fulvestrant may be the optimal treatment for HR+/HER2– postmenopausal women with ABC after disease progression following endocrine therapy. Keywords: advanced breast cancer, endocrine therapy, targeted therapy, progression-free survival, objective response rate, network meta-analysi