Chemotherapy-Free Survival of CDK4/6 Inhibitor Combination Therapy or Endocrine Monotherapy as First-Line Treatment for HR+/HER2–Advanced Breast Cancer

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) significantly prolong progression-free survival (PFS) compared to endocrine monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2–) advanced breast cancer (ABC). However, research regarding chemotherapy-free survival (CFS) comparing CDK4/6i combination therapy and endocrine monotherapy in real-world settings is limited. This retrospective, multicenter observational study aimed to assess the noninferiority of CFS between CDK4/6i combination therapy and endocrine monotherapy as first-line treatments for patients with HR+/HER2– ABC. The primary endpoint was CFS (noninferiority margin for comparison: 1.2). Among 443 patients (monotherapy: 318; CDK4/6i: 125), no significant difference was observed in median CFS after adjusting for patient background using inverse probability of treatment weighting (monotherapy: 35 months; CDK4/6i: 30 months; hazard ratio: 0.93; 95% confidence interval, 0.70–1.23). In the favorable group (patients with a performance status of 0 and no liver metastasis), those with either de novo stage IV disease or a disease-free interval of ≥ 60 months had a median CFS of 48 months for endocrine monotherapy and 44 months for CDK4/6i combination therapy. In HR+/HER2– ABC, the endocrine monotherapy group did not show noninferiority in CFS compared with the CDK4/6i combination group, with a small difference.