Background: Cyclin‐dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard‐of‐care for patients with hormone receptor‐positive, human epidermal growth factor receptor‐2 negative (HR+/HER2−) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib‐based ET in Chinese patients with HR+/HER2− MBC.Methods: From 414 consecutive patients with HR+/HER2− MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease‐free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression‐free survival (PFS) compared using the Kaplan–Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group.Results: The median PFS was 6.0 months (95% confidence interval [CI]: 3.94–8.06) in abemaciclib group and 4.0 months (95% CI, 2.52–5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first‐line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd‐line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069).Conclusion: Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2− MBC after progression on prior palbociclib‐based therapy in addition to chemotherapy.

We retrospectively analyzed consecutive patients with HER2-positive metastatic breast cancer who received T-DXd at a single Chinese cancer center between March 2023 and March 2026. Progression-free survival (PFS), overall survival (OS), systemic and intracranial response, safety, prognostic factors, and exploratory subsequent treatment strategies were assessed. Among 173 eligible patients, 80.3% had received prior HER2-directed TKIs and 41.6% had CNS metastases. After a median follow-up of 14.3 months, median PFS and OS were 14.1 and 31.1 months, respectively. The objective response rate was 54.5% among 154 patients with measurable systemic disease, while the CNS objective response rate was 46.3% among 67 patients with measurable CNS lesions. Among patients with measurable CNS lesions, the CNS-ORR was comparable between patients with and without peri-T-DXd local treatment (53.8% vs. 44.4%, p = 0.21). Greater prior treatment exposure was associated with shorter PFS, whereas HER2 IHC 3+ disease was independently associated with longer OS and showed a trend toward improved PFS compared with HER2 IHC 2+/FISH-positive disease. Interstitial lung disease occurred in 13 patients (7.5%), all grade 1–2. Among 148 patients included in the maintenance analysis, 23 switched to alternative maintenance regimens after initial benefit from T-DXd. In an exploratory analysis, no statistically significant differences in PFS or OS were observed between patients who continued T-DXd and those who switched to maintenance therapy. However, these findings require cautious interpretation because of immortal-time bias, selection bias, and limited sample size. T-DXd demonstrated clinically meaningful systemic and intracranial activity with manageable toxicity in this heavily pretreated real-world cohort.