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.

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.