Recently, Hengrui Medicine received the National Medical Products Administration issued a "notice of acceptance", the company submitted the drug marketing authorization application of pyrrotinib maleate tablets was accepted by the National Food and Drug Administration. The proposed indication for marketing is pyrrotinib in combination with trastuzumab and docetaxel in patients with epidermal growth factor receptor 2 (HER2) -positive recurrent or metastatic breast cancer who have not received anti-HER2 therapy in advanced stages.
Pyrrotinib is a small molecule, irreversible, pan-Erbb receptor tyrosine kinase inhibitor independently developed by Hengrui Pharmaceutical. It is also the first HER1/HER2/HER4 targeted drug independently developed in China. This new indication is based on a randomized, double-blind, parallel-controlled, multicenter phase III study (PHILA study No. HR-BLTN-III-MBC-C). The results showed that pyrrotinib maleate combined with trastuzumab and docetaxel significantly prolonged progression-free survival (PFS) compared with placebo combined with trastuzumab and docetaxel in patients with HER2-positive breast cancer who had not received any systematic antitumor therapy at the relapsed/metastatic stage.
About the PHILA
PHILA research is an evaluation for maleic acid pyrrole, combined by bead sheet resistance and more west he match compared to placebo combined by bead sheet resistance and many west he match first-line treatment/metastatic breast cancer HER2 positive recurrence of randomized, double-blind, parallel-group, multicenter, phase III clinical study by academician of Chinese academy of medical sciences tumor hospital Xu Bing river as the main researchers, Forty centers across the country participated. The study was initiated in April 2019, with a total of 590 subjects enrolled in 1:1 randomization. The primary end point was investigator-assessed progression-free survival (PFS), and secondary end points included independent imaging Evaluation Board (IRC) -assessed PFS, overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), objective response duration (DOR), and safety. In August 2022, the interim analysis of the primary end point PFS was completed, and the Independent Data Monitoring Committee (IDMC) determined that the interim analysis of the primary end point met the prespecified criteria of superiority.
The findings were presented as a brief oral presentation at the 2022 annual meeting of the European Society of Medical Oncology (ESMO) in September 2022. The results of the study showed [1] that in terms of the primary end point, the PFS assessed by the investigators in the pyrrotinib group reached 24.3 months (vs 10.4 months in the control group, HR=0.41). For secondary end points, PFS assessed by an independent review committee was 33.0 months in the pyrrotinib group (vs. 10.4 months in the control group, HR=0.35), ORR was 82.8% in the pyrrotinib group and 70.6% in the control group, and median DoR was 25.9 months and 9.5 months, respectively. In terms of safety, the study was generally well tolerated, adverse effects were manageable, the overall safety data were consistent with known safety characteristics of the study drug, and no new safety signals were identified.
About pyrrolitinib
Pyrrotinib is an oral HER1/HER2/HER tyrosine kinase inhibitor independently developed by Hengrui Pharmaceutical and has intellectual property rights. It is the first independently developed HER1/HER2/HER4 targeted drug in China.
As a small-molecule, irreversible, pan-Erbb receptor tyrosine kinase inhibitor, pyrrotinib inhibits tumor cell growth by preventing the formation of homogeneous and heterogeneous dimers of epidermal growth factor (EGFR) and HER2 in tumor cells, inhibiting their own phosphorylation, and blocking the activation of downstream signaling pathways.
In 2018, pyrrotinib was conditionally approved for marketing based on phase II clinical study data, and was included in the national medical insurance in 2019. In 2020, pyrrolitinib received full approval from the State Food and Drug Administration for marketing in combination with capecitabine in HER2-positive patients with recurrent or metastatic breast cancer who had received trastuzumab, based on the results of two important phase III studies (PHENIX, PHOEBE). In May 2022, pyrrotinib was approved for a second indication, in combination with trastuzumab and docetaxel, for neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer.
