Efficacy and safety of dalpiciclib plus fulvestrant and pyrotinib in HR+, HER2-low advanced breast cancer following CDK4/6 inhibitor and aromatase inhibitor: A Bayesian optimal phase Ⅱ trial.

e13060 Background: Cross-line treatment with CDK4/6 inhibitors (CDK4/6i) is a challenging topic in breast cancer (BC). The postMONARCH study and the MAINTAIN study provided evidence for re-challenging the CDK4/6i regimen. This study aims to assess the efficacy and safety of dalpiciclibplus fulvestrant and pyrotinib in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2) low advanced BC, who have experienced disease progression after treatment with CDK4/6i and aromatase inhibitor (AI). Methods: This single-arm Bayesian optimal phase Ⅱ trial included adults with HR+, HER2-low advanced BC, disease progression after treatment with CDK4/6i and AI. Enrolled patients received oral dalpiciclib (125 mg per day for 3 weeks and one week off) plus fulvestrant (500 mg, administered intramuscularly every four weeks) and oral pyrotinib (320 mg once daily) until intolerance or disease progression. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety and biomarker analysis. Results: From May 2023 to November 2024, a total of 30 patients were enrolled in this study. The median age of the patients was 50.5 years (IQR: 42.5-57.3). Among these patients, 21 (70.0%) received abemaciclib, and 10 (33.3%) received palbociclib and ribociclib. The median duration of prior treatment with CDK4/6i was 13 months (95% CI: 10.3-15.7). At data cut-off on January 10 2025, a total of 29 patients were evaluated for efficacy, with an ORR of 20.7% (6/29). The median follow-up period was 14.3 months (IQR: 6.7-14.7), and the median PFS (mPFS) was 4.2 months (95% CI: 1.4-7.0). Among the included patients, those ≤50 years and > 50 years each accounted for 50%, mPFS was 3.1 months (95% CI: 1.1-5.1) and 7.7 months (95% CI: 2.2-13.2), respectively. Patients with HER2 expression of 1 + were 57% and 2 +/ISH-were 43%, the mPFS was 5.0 months (95% CI: 1.4-8.6) and 3.8 months (95% CI: 1.2-6.4), respectively. The mPFS was 3.8 months (95% CI: 2.3-5.3), 5.0 months (95% CI: 0-10.3) and 2.0 months (95% CI: 1.0-3.0) in patients previously treated with abemaciclib, palbociclib and ribociclib, respectively. Among 16 patients with genetic testing, the mPFS was 1.6 months (95% CI: 1.1-2.1) for patients with gene mutation (7 cases) and 7.8 months (95% CI: 4.2-11.4) for wild-type patients (9 cases). The most common adverse events reported were diarrhea and neutropenia. Grade 3 treatment-related adverse events (TRAEs) were reported in 56.7% (17/30) of the patients, and no grade 4 TRAEs were observed. Conclusions: Our results indicated that dalpiciclib plus fulvestrant and pyrotinib achieves promising efficacy and safety in in HR+, HER2-low advanced BC patients following CDK4/6i and AI treatment. Clinical trial information: NCT05806671 .