Efficacy and Safety of Abemaciclib in Combination With Endocrine Therapy for HR+/HER2− Advanced or Metastatic Breast Cancer

Objectives: Breast cancer, particularly the hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) subtype, remains a major global health concern. Abemaciclib, a CDK4/6 inhibitor, has shown promising results in treating advanced cases. This study comprehensively assesses the efficacy and safety of abemaciclib in combination with endocrine therapy for HR+/HER2− advanced or metastatic breast cancer. Methods: Following PRISMA guidelines, a systematic review and meta-analysis was conducted. A thorough literature search was conducted on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov til December 2023. Inclusion criteria encompassed randomized controlled trials and retrospective cohort studies reporting on abemaciclib in approved doses, either as monotherapy or in combination. Outcome assessments included progression-free survival (PFS), overall response rate (ORR), side effects/adverse effects (SE/AE), and overall survival (OS). Quality assessment utilized Cochrane’s revised risk of bias tool and Newcastle-Ottawa scale. Results: Pooled results of 22 studies involving 14,010 patients revealed that abemaciclib significantly improved PFS (hazard ratio=0.53; 95% CI: 0.48-0.59; P =0.00; I 2 =0%), ORR (risk ratio=2.31; 95% CI: 1.93-2.75; P =0.00; I 2 =0%), and OS (risk ratio=0.76 (95% CI: 0.65-0.87; P =0.001; I 2 =0%). However, abemaciclib increased the risk of adverse events in the fulvestrant and nonsteroidal aromatase inhibitor (NSAI) combinations, respectively. Conclusions: Abemaciclib, particularly in combination with fulvestrant, emerges as an effective therapeutic option for HR+/HER2− advanced or metastatic breast cancer, improving PFS and OS. The higher toxicity profile warrants cautious use, especially in treatment-naive patients.