On April 22, 2023, Jiangsu Hengrui Medicine Co., Ltd. received the Drug Registration Certificate issued by the National Medical Products Administration (NMPA), approving its independently developed human epidermal growth factor receptor 1/2/4 (HER1/HER2/HER4) targeted drug pyrotinib (Aini) in combination with trastuzumab and docetaxel for the first-line treatment of HER2-positive advanced breast cancer.
This represents China's first approved dual-target combination regimen consisting of a receptor tyrosine kinase inhibitor (TKI) and a macromolecular antibody drug for advanced breast cancer therapy, bringing a novel treatment choice to patients with advanced breast cancer. The newly approved indication specifies that this product, in combination with trastuzumab and docetaxel, is indicated for the treatment of patients with HER2-positive, relapsed or metastatic breast cancer who have not received anti-HER2 therapy in the advanced stage.
The approval of this indication for marketing is based on the results of a randomized, double-blind, parallel-controlled, multicenter Phase III clinical trial (PHILA study, trial number: HR-BLTN-III-MBC-C). Study data demonstrated that for patients with HER2-positive breast cancer who had not received any anti-HER2 therapy in the advanced stage, treatment with pyrotinib maleate tablets combined with trastuzumab and docetaxel yielded significant progression-free survival (PFS) benefits with a tolerable safety profile. The primary endpoint, investigator-assessed PFS, reached a median of 24.3 months, making this combination the regimen with the longest confirmed PFS benefit for the first-line treatment of HER2-positive advanced breast cancer among Phase III trial-validated therapies to date.
The approval of pyrotinib in combination with trastuzumab and docetaxel for the first-line treatment of advanced HER2-positive breast cancer is grounded in the breakthrough findings of the PHILA study. The research outcomes were presented as an oral report at the 2022 European Society for Medical Oncology (ESMO) Annual Congress, attracting close attention from experts and scholars worldwide.
The PHILA study is a Phase III clinical trial designed to evaluate the efficacy and safety of pyrotinib plus trastuzumab and docetaxel versus placebo plus trastuzumab and docetaxel as first-line treatment for HER2-positive relapsed/metastatic breast cancer. Led by Principal Investigator Academician Xu Binghe from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, the trial was jointly conducted across 40 clinical centers nationwide, enrolling a total of 590 participants. In August 2022, the study completed the interim analysis of its primary endpoint (PFS), and the Independent Data Monitoring Committee (IDMC) concluded that the interim results met the pre-specified superiority criteria in the trial protocol.
The positive results of the PHILA study have confirmed that the dual-target combination of "TKI plus macromolecular antibody drug" delivers substantial clinical benefits and a favorable safety profile as a first-line treatment option for HER2-positive advanced breast cancer.
Shortly after the PHILA study results were announced in September 2022, the PyHT regimen (pyrotinib + trastuzumab + docetaxel) was incorporated into the first-line treatment recommendations for HER2-positive advanced breast cancer in two key guidelines: it was listed as a Category IB recommended regimen in the Standard Guidelines for Diagnosis and Treatment of Advanced Breast Cancer in China (2022 Edition), and designated as a "consideration regimen" in the CACA Guidelines for Diagnosis and Treatment of Breast Cancer (2022 Concise Edition).
In the updated CSCO Guidelines for Diagnosis and Treatment of Breast Cancer released in April 2023, this combination was further upgraded to a Category I recommendation (2A) for patients with HER2-positive advanced breast cancer who are sensitive to trastuzumab-based therapy.
