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Dalpiciclib plus fulvestrant and pyrotinib in HR+/HER2-low advanced breast cancer after progression on CDK4/6 inhibition (DapPLE-HER): a Bayesian optimal phase II study

Year: 2025

Type: article

Abstract: BACKGROUND: The optimal management strategy for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) patients after progression on cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) remains undefined. This study aimed to evaluate the efficacy and safety of a combination therapy of dalpiciclib, fulvestrant, and pyrotinib in HR+/HER2-low advanced BC patients with progression on prior CDK4/6i treatment. METHODS: This was an open-label, single-arm, multicenter, Bayesian optimal phase II exploratory study. Eligible patients received dalpiciclib (125 mg/day, 3 weeks on/1 week off), fulvestrant (500 mg intramuscularly every 4 weeks), and pyrotinib (320 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: A total of 30 patients were enrolled in this study. At a median follow-up of 14 months, the median PFS was 4.23 months (95% CI: 2.47-7.90). The ORR was 20.7% (95% CI: 9.8%-38.4%) and the DCR was 51.7% (95% CI: 34.4%-68.6%). The common adverse events (AEs) were diarrhea (83.3%) and decreased white blood cell count (70.0%). Grade 3 AEs were infrequent, and no grade ≥4 AEs were observed. Subgroup analysis revealed that mutation status was significantly associated with PFS ( P = 0.004). CONCLUSION: The combination of dalpiciclib, fulvestrant, and pyrotinib demonstrated modest efficacy with a manageable safety profile in HR+/HER2-low advanced BC patients who had progressed on prior CDK4/6i therapy. This novel regimen demonstrated exploratory efficacy and a favorable safety profile, warranting further validation in future randomized controlled studies.

Source: International Journal of Surgery

DOI: 10.1097/js9.0000000000003208