Efficacy and safety of CDK4/6 inhibitors in HER2-positive breast cancer: A systematic review and meta-analysis.

Abstract

e13013 Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including Palbociclib, Ribociclib, and Abemaciclib, have demonstrated significant efficacy in hormone receptor-positive (HR+), HER2-negative breast cancer. However, their role in HER2-positive (HER2+) breast cancer remains under active investigation. This systematic review and meta-analysis aim to assess the efficacy and safety of CDK4/6 inhibitors in HER2+ breast cancer. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted using PubMed, Cochrane Library, and ClinicalTrials.gov databases with MeSH terms and keywords such as “CDK4/6 inhibitors,” “HER2-positive breast cancer,” and “clinical trials.” Out of 253 reports, 25 studies met the inclusion criteria. Extracted data included baseline demographics, study design, treatment regimens, tumor characteristics, line of therapy, and outcomes. Outcome estimates from individual studies were logit-transformed and pooled using a random-effects model in RStudio. Forest plots were generated to visualize pooled results with 95% confidence intervals (CI). Results: A total of 362 patients from five included studies were analyzed. The age of patients ranged from 34 to 89 years, with the majority being postmenopausal women. The median number of prior therapies was 3, primarily targeting metastatic disease, with one study focusing on neoadjuvant therapy. Follow-up durations varied from 6 to 24 months. CDK4/6 inhibitors evaluated included Abemaciclib, Palbociclib, and Ribociclib, in combination with HER2-targeted and endocrine therapies. The pooled overall response rate (ORR) was 28.97% (95% CI: 5.20–75.21; I² = 83.6%, p < 0.0001), with complete responses in 5.25% (95% CI: 0.00–26.22; I² = 93.8%, p < 0.0001) and partial responses in 16.89% (95% CI: 4.94–33.18; I² = 76.5%, p = 0.0019). Progression-free survival (PFS), reported in four studies, averaged 7.01 months (95% CI: 3.10–10.84; I² = 99.8%). Stable disease (SD) was achieved in 36.80% (95% CI: 13.48–63.64; I² = 91.2%, p < 0.0001), while progressive disease (PD) occurred in 29.03% (95% CI: 7.11–57.28; I² = 86.7%, p < 0.0001). Neutropenia was the most common adverse event, affecting 42.95% of patients (95% CI: 22.83–64.27; I² = 91.3%, p < 0.0001), followed by diarrhea, fatigue, and alopecia. Conclusions: CDK4/6 inhibitors combined with anti-HER2 therapies showed moderate efficacy in HER2+ breast cancer, offering disease control in most patients, slowing tumor progression, and providing a chemotherapy-free option with manageable toxicity. However, they are not yet standard treatment. Further studies are needed to confirm these findings and establish optimal treatment protocols.