Efficacy and Safety of AKT Inhibitors in HR+/HER2- Breast Cancer or Metastatic TNBC: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Purpose This study aims to investigate the impact of AKT inhibitors (Capivasertib and Ipatasertib) on the efficacy and safety of patients with HR+/HER2- breast cancer or metastatic TNBC. Methods A comprehensive search for relevant randomized clinical trials (RCTs) of AKT inhibitors were conducted through PubMed, Embase, and Cochrane Library. The meta-analysis included five studies with a total of 1304 patients. Outcome indicators such as progression-free survival (PFS), adverse events (AEs), overall survival (OS), duration of response (DOR), objective response rate (ORR), and clinical benefit rate (CBR) were analyzed using Review Manager 5.4.1. Results Patients treated with AKT inhibitors showed a significant improvement in PFS compared to those without (MD = 2.39; 95% CI: 1.06, 3.73; p = 0.0005; I² = 55%). However, the incidence of some dangerous AEs increased, including infection (OR = 1.72; 95% CI: 1.09, 2.72; p = 0.02; I² = 0%) and hyperglycemia (OR = 3.07; 95% CI: 1.36, 6.93; p = 0.007; I² = 63%). Conclusions AKT inhibitors significantly prolonged the survival of patients with metastatic TNBC and HR+/HER2- breast cancer. Nevertheless, the occurrence of AEs, such as infection and hyperglycemia, during AKT inhibitor treatment suggests the need for careful and rational drug usage based on specific patient conditions.