Twenty to 30 percent of breast cancer patients are HER2, or human epidermal growth factor receptor 2, positive. HER2-positive breast cancer is highly malignant, has rapid disease progression, is prone to recurrence and metastasis, and has a poor prognosis.
Pyrotinib, a new drug developed in China that works against HER2 targets, was launched in China in August 2018. Small studies have initially shown that for HER2-positive advanced breast cancer, pyrrolitinib is more than 80% effective in first-line targeted therapy.
Irreversibly inhibiting dual targets, pyrrolitinib fights breast cancer this way
Pyrrolitinib has a two-fold mechanism of action: dual-target, irreversible.
The dual-target approach means that pyrrolitinib inhibits both HER2 and HER1, two targets that are members of the HER family and are highly expressed in some breast cancers, and when activated by tyrosine kinases, HER2 and HER1 can send growth orders to cells and play an important role in tumor cell proliferation. Pyrrolitinib is a tyrosine kinase inhibitor (TKI) that inhibits the activation of HER2 and HER1 by tyrosine kinases, thus preventing HER2 and HER1 from sending growth orders to cells. This is the mechanism by which pyrrolitinib inhibits the development and progression of breast cancer. Dual-target inhibition makes its inhibition of tumor growth signaling pathways potentially more potent.
Irreversible inhibition of tyrosine kinases is also another feature of pyrrolitinib, which permanently inactivates the action of tyrosine kinases on HER2 and HER1, thereby increasing the durability of the drug’s action and potentially reducing tumor resistance.
First-line monotherapy effective in more than 80% of patients
The first phase I clinical study of pyrrolitinib in breast cancer was conducted by researchers in China. A total of 38 patients with HER2-positive metastatic breast cancer were enrolled in the study, all of whom had not received anti-HER2 TKI therapy.
The results were that patients treated with pyrrolizidine had an overall remission rate of 50% and a clinical benefit rate of 61.1%, meaning that more than 60% of patients achieved complete remission, partial remission, or stable disease for ≥24 weeks. Further analysis revealed an overall effectiveness rate of 83.3% in patients who had never had trastuzumab (Trastuzumab) before. The median progression-free survival of patients receiving pyrrolizumab in this study was 35.4 weeks. This shows that pyrrolizumab is promising for HER2-positive metastatic breast cancer.
Safety-wise, patients showed good tolerability of pyrrolitinib. Common adverse reactions were diarrhea (44.7%), nausea (13.2%), mouth ulcers (13.2%), malaise (10.5%), and leukopenia (10.5%), with the only Grade 3 adverse reaction being diarrhea.
What is the status of pyrrolitinib in China?
What is the status of pyrrolizidine in China?
The State Food and Drug Administration (CFDA) has now approved the marketing of pyrrolitinib.
Exploration of the use of pyrrolitinib in breast cancer is still underway. We know from our drug clinical trial registration and information disclosure platform that there are two phase III clinical studies of pyrrolitinib for HER2-positive advanced breast cancer in China, with 350 and 240 HER2-positive metastatic breast cancer patients, respectively.
Patients in the study will likely receive pyrrolitinib in combination with capecitabine or capecitabine alone (No.: CTR20160442), and in another study the treatment regimen will be pyrrolitinib in combination with capecitabine or lapatinib in combination with capecitabine (No.:CTR20170251). All of these studies are currently in patient recruitment.
Summary
For first-line treatment of HER2-positive advanced breast cancer, pyrrolitinib is effective in more than 80% of patients. Several more studies are currently being explored in China, and we look forward to bringing more detailed data to bring survival benefits to more eligible patients.