Efficacy, Safety, and Prognostic Factors of Dalpiciclib Combined with Endocrine Therapy After Progression on CDK4/6 Inhibitors in Patients with HR+/HER2- Advanced Breast Cancer: A Retrospective Study.

Background: While the combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) has established efficacy as first-line treatment for HR+/HER2- advanced breast cancer (ABC), resistance remains a critical clinical challenge. Dalpiciclib, a novel Chinese-developed CDK4/6i, has shown promising results in first-line therapy, yet data on its efficacy following progression on prior CDK4/6i is limited. Methods: This retrospective, multicenter study enrolled 58 patients with HR+/HER2- ABC who experienced disease progression after prior CDK4/6i therapy and received dalpiciclib combined with ET between July 2022 and October 2024. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Subgroup analyses were performed based on baseline clinical characteristics and prior treatment histories. Results: The median PFS was 6.3 months (95% CI: 5.2-11.0). The ORR and DCR were 8.6% and 32.8%, respectively. Patients with liver metastases exhibited significantly shorter PFS compared to those without (4.2 vs 8.0 months, Conclusion: Dalpiciclib combined with endocrine therapy demonstrates clinical efficacy and a manageable safety profile as a cross-line treatment for HR+/HER2- ABC patients who progressed on prior CDK4/6i. Subgroups including those without liver metastases, with secondary endocrine resistance, and receiving sequential CDK4/6i therapy appear to derive greater benefit. These findings support dalpiciclib as a viable cross-line therapeutic option, warranting further prospective validation.