The efficacy and safety of targeted therapy plus fulvestrant in postmenopausal women with hormone-receptor positive advanced breast cancer: A meta-analysis of randomized-control trials

Objective: To evaluate the efficacy and safety of targeted therapy plus fulvestrant for postmenopausal patients with hormone receptor-positive advanced breast cancer. Methods: Pubmed, Embase and Web of Science databases were systematically searched on February 26, 2018. Eligible studies were screened according to selection criteria, and two reviewers independently extracted outcome data which included progression-free survival, overall survival, objective response rate, clinical benefit rate and toxicities. RevMan 5.3 and STATA 11.0 software were used to conduct meta-analysis. Results: Thirteen articles including twelve randomized-control trials fulfilled selection criteria. There was no evidence regarding the existence of publication bias and high-risk bias of quality in the selected studies. In previously endocrine therapy-treated postmenopausal patients with hormone-receptor positive advanced breast cancer, the PFS (HR = 0.77, 95%CI: 0.66–0.91) and ORR (RR = 1.78, 95%CI: 1.35–2.34) of combination therapy group were significantly higher than that from fulvestrant monotherapy group. Besides, a statistically significant difference in PFS was found across the two arms in postmenopausal women with PIK3CA-mutant ctDNA tumor (HR = 0.52, 95% CI: 0.39–0.69). Moreover, the risk of adverse events (RR = 1.09, 95%CI: 1.05–1.13), CTCAE≥3 (RR = 1.97, 95%CI: 1.49–2.60) and discontinuation due to adverse events (RR = 4.91, 95%CI: 3.37–7.15) were also significantly different between two treatment groups. Sensitivity analysis showed PLOMA-3 trial was an important factor of heterogeneity. Discussion: Even though the combination of targeted therapy plus fulvestrant improved PFS and increased ORR in advanced breast cancer patients, the toxicities of combination therapy were also higher than fulvestrant monotherapy. Further studies related to inhibitors targeting the specific signaling pathway or receptors are urgently needed, and more efforts concerning precision medicine of targeted therapy plus endocrine therapy should be taken to improve the clinical benefits.