Real-world outcomes of CDK4/6 inhibitors in combination with endocrine therapy as first-line treatment for HR-positive/HER2-negative advanced breast cancer: multicenter evidence from China

Abstract Background CDK4/6 inhibitors combined with endocrine therapy constitute the global first-line standard of care for HR + /HER2 − advanced breast cancer (ABC), yet no head-to-head trials comparing different CDK4/6 inhibitors have been conducted, and real-world comparative data in Chinese patients is currently unavailable. Methods We conducted a multicenter retrospective study of 341 Chinese patients with HR + /HER2 − ABC who received first-line palbociclib ( n = 177), abemaciclib ( n = 114), or dalpiciclib ( n = 50) from 2018 to 2023. The primary endpoint was progression-free survival (PFS); secondary endpoints included safety, tolerability, and objective response rate. Results Median PFS was 24 months for palbociclib and 32 months for abemaciclib, while median PFS for dalpiciclib was not reached. Abemaciclib significantly prolonged PFS compared with palbociclib (palbociclib vs. abemaciclib: adjusted HR = 1.86, 95% CI 1.24–2.79), with consistent benefits in premenopausal, postoperative recurrence, progesterone receptor–positive, HER2-low, luminal B, visceral metastasis, and endocrine-resistant subgroups (all p < 0.05). Overall tolerability was comparable, though palbociclib and dalpiciclib were associated with higher myelosuppression, whereas abemaciclib more frequently caused low-grade diarrhea. Conclusions This is the larger real-world study to compare different CDK4/6 inhibitors in Chinese HR + /HER2 − ABC patients. Abemaciclib demonstrated a significant PFS advantage over palbociclib while maintaining a manageable safety profile, particularly benefiting biologically aggressive or treatment-resistant subgroups. These findings provide population-specific evidence to guide individualized CDK4/6 inhibitor selection and refine first-line treatment strategies for Chinese patients with HR + /HER2 − ABC.