CDK4/6 inhibitors versus PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: An updated systematic review and network meta-analysis of 28 randomized controlled trials

作者：Hangcheng Xu, Yan Wang, Yiqun Han, Yun Wu, Jiayu Wang, Binghe Xu · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.956464 · 被引用次数：28 · 研究领域：Advanced Breast Cancer Therapies、Cancer Treatment and Pharmacology、HER2/EGFR in Cancer Research

Background: Updated evidence was required to compare the efficacy and safety of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors for patients with hormone receptor-positive and HER2-negative metastatic breast cancer. Methods: A systematic review and network meta-analysis was conducted utilizing data from randomized controlled trials (RCTs) that contained interventions of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were primary outcomes of interest. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% credible intervals (CrIs) were used to assess the survival outcomes and safety profiles, respectively. Results: A total of 28 RCTs with 12,129 participants were included. Pooled analysis showed that CDK4/6 inhibitors significantly prolonged PFS than PI3K/AKT/mTOR inhibitors (HR, 0.81; 95% CrI, 0.69-0.94), whereas no significant differences were detected regarding OS. After balancing the treatment lines and metastatic sites, the superiority of CDK4/6 inhibitors only appeared in the visceral and non-visceral subgroups. Among CDK4/6 inhibitors, abemaciclib was significantly better than others in ≥3 grade neutropenia (OR, 0.04; 95% CrI, 0.01-0.15). The incidence of stomatitis and digestive disorders was different among diverse kinds of PI3K/AKT/mTOR inhibitors. D...