biostudies-literatureZhao JScience and Technology Planning Project of Guangdong ProvinceNational Natural Science Foundation of ChinaNational Key Research and Development Program of Chinae70031https://www.ebi.ac.uk/biostudies/studies/S-EPMC11661908biostudies-literatureUnknown6(1)This multicenter, single-arm, phase II clinical trial (NCT04034589) evaluated the efficacy and safety of pyrotinib combined with fulvestrant in patients with HR-positive/HER2-positive metastatic breast cancer who had experienced trastuzumab treatment failure. A total of 46 patients were enrolled, receiving pyrotinib orally once daily and fulvestrant intramuscularly on days 1 and 15 of cycle 1, followed by monthly doses on day 1. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. The median PFS was 18.2 months (95% CI, 11.9-31.1) overall, 19.5 months (95% CI, 10.6-NA) for those receiving the combination as first-line therapy, and 18.4 months (95% CI, 16.7-NA) for patients with brain metastases. Median OS was not reached, with a 3-year OS rate of 75.2% (95% CI, 62.8-90.2%). The ORR was 32.5%, and the DCR was 97.5%. Responses were observed in patients with low tumor mutation burden and <i>ZNF217</i> mutation. Importantly, no grade 4 or higher treatment-related adverse events or deaths were reported, indicating a favorable safety profile. In conclusion, the combination of pyrotinib and fulvestrant demonstrated promising antitumor activity and acceptable safety in HR-positive/HER2-positive metastatic breast cancer patients.MedCommCombined pyrotinib and fulvestrant for hormone receptor-positive and HER2-positive metastatic breast cancer: A multicenter, single-arm, phase II trial.PMC116619088207175482271793822732042023B121206001382203141821028652023YFE0204000Ren WYuan PZhang KZhang LZeng YChai JGui XDing LYue JZou GYang YCai YChen YWu WLuo SYao HWang YZhao JYuan ZYu YChen TfalseCombined pyrotinib and fulvestrant for hormone receptor-positive and HER2-positive metastatic breast cancer: A multicenter, single-arm, phase II trial.This multicenter, single-arm, phase II clinical trial (NCT04034589) evaluated the efficacy and safety of pyrotinib combined with fulvestrant in patients with HR-positive/HER2-positive metastatic breast cancer who had experienced trastuzumab treatment failure. A total of 46 patients were enrolled, receiving pyrotinib orally once daily and fulvestrant intramuscularly on days 1 and 15 of cycle 1, followed by monthly doses on day 1. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. The median PFS was 18.2 months (95% CI, 11.9-31.1) overall, 19.5 months (95% CI, 10.6-NA) for those receiving the combination as first-line therapy, and 18.4 months (95% CI, 16.7-NA) for patients with brain metastases. Median OS was not reached, with a 3-year OS rate of 75.2% (95% CI, 62.8-90.2%). The ORR was 32.5%, and the DCR was 97.5%. Responses were observed in patients with low tumor mutation burden and <i>ZNF217</i> mutation. Importantly, no grade 4 or higher treatment-related adverse events or deaths were reported, indicating a favorable safety profile. In conclusion, the combination of pyrotinib and fulvestrant demonstrated promising antitumor activity and acceptable safety in HR-positive/HER2-positive metastatic breast cancer patients.2025-01-01T00:00:00Z2025 Jan2026-06-01T19:51:20.52Z2025-04-04T20:28:22.196ZS-EPMC116619083971245510.1002/mco2.70031