Palbociclib, trastuzumab, pyrotinib and fulvestrant in patients with brain metastasis from ER/PR positive, HER-2 positive breast cancer: Report from an interim analysis of a multicenter, prospective study in China

e13032 Background: HER2-positive breast cancer patients are at a high risk of developing metastases in brain. Effective treatment should involve anti-HER2 targeted therapy. This aim of this study is to evaluate the activity of the chemo-free combination of palbociclib, trastuzumab and pyrotinib with fulvestrant in ER positive, HER2-positive breast cancer patients with brain metastasis. Methods: We did a multi-center, prospective trial in three hospitals in China. Female patients older than 18 years who had whole brain radiotherapy-naive ER/PR positive, HER2-positive brain metastases with an Eastern Cooperative Oncology Group performance status of 0–2 were treated with palbociclib, fulvestrant, combined with trastuzumab and pyrotinib, and until disease progression or intolerable adverse effects. The primary endpoint was objective response rate in the central nervous system (CNS), as assessed by investigator per the modified Response Evaluation Criteria In Solid Tumours (version 1.1). The study is still ongoing and recruiting. Here we report the results of an interim analysis. The study is registered with ClinicalTrials.gov, NCT04334330. Results: Between December 4, 2020 and November 2, 2022, 15 patients were enrolled. Eleven patients had prior exposure to trastuzumab. In the 14 patients who were evaluable for clinical response, the objective response rate in the CNS was 28.6%? (95% CI, 8.4% - 58.1%). At a median follow-up of 6.3 months (range, 2.1-14.3 months), the median PFS was 10.6 months (95%CI, 4.3 – 16.9 months). The time to progression in the CNS was 8.5 months (95%CI, 5.9 – 11.1 months). Conclusions: Combination of palbociclib, trastuzumab and pyrotinib with fulvestrant represents an active chemo-free treatment strategy in hormonal receptor positive, HER2-positive breast cancer patients with brain metastasis. Clinical trial information: NCT04334330 .