With regards to safety, First-line CDK4/6 inhibitors plus ET exhibited a greater likelihood of encountering SAEs (RR = 1.54, 95% CI: 1.30 to 1.82, P < 0.01) in comparison to ET.<h4>Conclusion</h4>The present meta-analysis reported comparative long-term outcomes of CDK4/6 inhibitors plus ET versus ET as first-line therapy for HR+/HER2-metastatic or advanced breast cancer. The gene discussed is ERBB2; the disease is breast cancer.