BMC Medicine (Aug 2023)

Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial

  • Jun Cao,
  • Yuee Teng,
  • Huiping Li,
  • Lili Zhang,
  • Quchang Ouyang,
  • Weimin Xie,
  • Yueyin Pan,
  • Zhenchuan Song,
  • Xiaoling Ling,
  • Xiaohong Wu,
  • Jingwei Xu,
  • Li Li,
  • Liping Ren,
  • Hong Wang,
  • Dongxian Zhou,
  • Jing Luo,
  • Xichun Hu

DOI
https://doi.org/10.1186/s12916-023-02999-0
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 10

Abstract

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Abstract Background Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer and primary resistance to trastuzumab have a poor clinical outcome and lack good evidence to inform clinical decision. This study investigated the efficacy and safety of pyrotinib plus capecitabine in this population. Methods This phase 2 trial was conducted at 16 sites in China. Patients received oral pyrotinib 400 mg once daily and capecitabine 1000 mg/m2 twice a day on days 1–14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Between June 2019 and September 2021, 100 patients were enrolled with a median age of 51 years (range, 24–69). All patients had been treated with trastuzumab and 21 (21.0%) patients had prior use of pertuzumab. As of August 31, 2022, the median follow-up duration was 20.1 months (range, 1.3–38.2). The median PFS was 11.8 months (95% confidence interval [CI], 8.4–15.1), which crossed the pre-specified efficacy boundary of 8.0 months. The objective response rate was 70.0% (70/100), with a median duration of response of 13.8 months (95% CI, 10.2–19.3). The disease control rate was 87.0% (87/100). The median overall survival was not reached. The most common grade ≥ 3 treatment-emergent adverse event was diarrhea (24 [24.0%]). No treatment-related deaths occurred. Conclusions Pyrotinib plus capecitabine can be considered to be a treatment option in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab. Even in the era of modern anti-HER2 treatments, this clinical setting warrants more investigations to meet unmet needs. Trial registration ClinicalTrials.gov, NCT04001621. Retrospectively registered on June 28, 2019.

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