Journal Article

Pyrotinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (PERSIST): A multicenter phase II trial

Hao, Jing, Cao, Feilin, Feng, Qingjing, Ji, Xiaochun, Wang, Ouchen, Tao, Deyou, Huang, Shifen, Lin, Wei, Ma, Zhaosheng, Shu, Jingde, Wu, Weizhu, Li, Zhanwen, Zhou, Jichun, Cui, Binbin, Shi, Dongbo, Zhu, Xiaotao, Wu, Zenggui

2025

Overview

Approximately one-third of patients with HER2-positive breast cancer experienced recurrence within 10 years after receiving 1 year of adjuvant trastuzumab. The ExteNET study showed that 1 year of extended adjuvant neratinib after trastuzumab-based adjuvant therapy could reduce invasive disease-free survival (iDFS) events compared with placebo. This study investigated the efficacy and safety of pyrotinib, an irreversible pan-HER receptor tyrosine kinase inhibitor, after trastuzumab-based adjuvant therapy in patients with high-risk, HER2-positive early or locally advanced breast cancer. This multicenter phase II trial was conducted at 23 centers in China. After enrollment, patients received 1 year of extended adjuvant pyrotinib (400 mg/day), which should be initiated within 6 months after the completion of 1-year adjuvant therapy (trastuzumab alone or plus pertuzumab). The primary endpoint was 2-year iDFS rate. Between January 2019 and February 2022, 141 eligible women were enrolled and treated. As of October 10, 2022, the median follow-up was 24 (interquartile range, 18.0-34.0) months. The 2-year iDFS rate was 94.59% (95% confidence interval [CI]: 88.97-97.38) in all patients, 94.90% (95% CI: 86.97-98.06) in patients who completed 1-year treatment, 90.32% (95% CI: 72.93-96.77) in patients who completed only 6-month treatment, 96.74% (95% CI: 87.57-99.18) in the hormone receptor (HR)-positive subgroup, 92.77% (95% CI: 83.48-96.93) in the HR-negative subgroup, 96.88% (95% CI: 79.82-99.55) in the lymph node-negative subgroup, 93.85% (95% CI: 86.81-97.20) in the lymph node-positive subgroup, 97.30% (95% CI: 82.32-99.61) in patients with adjuvant trastuzumab plus pertuzumab, and 93.48% (95% CI: 86.06-97.02) in patients with adjuvant trastuzumab. The most common adverse events were diarrhea (79.4%), fatigue (36.9%), lymphocyte count decreased (36.9%), nausea (33.3%), and hand-foot syndrome (33.3%). Extended adjuvant pyrotinib administrated after trastuzumab-based adjuvant therapy showed promising efficacy in patients with high-risk HER2-positive breast cancer. The follow-up is ongoing to determine the long-term benefit. No external funding was received for this work. ClinicalTrials.gov: NCT05880927.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Acrylamides - administration & dosage / Acrylamides - adverse effects / Acrylamides - therapeutic use / Adjuvant therapy / Adjuvants / Adult / Aged / Aminoquinolines - administration & dosage / Aminoquinolines - adverse effects / Aminoquinolines - therapeutic use / Breast cancer / Breast Neoplasms - drug therapy / Cancer therapies / Cell number / Chemotherapy / Chemotherapy, Adjuvant - methods / China / Clinical trials / Diarrhea / Disease / Drug dosages / Epidermal growth factor / ErbB-2 protein / extended adjuvant therapy / Female / Gene amplification / human epidermal growth factor receptor 2 / Humans / invasive disease-free survival / Kinases / Lymph nodes / Lymphatic system / Lymphocytes / Medicine / Metastasis / Middle Aged / Oncology / Patients / Protein-tyrosine kinase receptors / pyrotinib / Receptor, ErbB-2 - metabolism / Trastuzumab / Trastuzumab - administration & dosage / Trastuzumab - therapeutic use / Treatment Outcome / Womens health