Formulation and Specifications: Tablets: 80mg, 160mg
Indications: Pyrrolitinib in combination with capecitabine is indicated for the treatment of patients with HER2-positive recurrent or metastatic breast cancer who have not previously received or have received trastuzumab. Patients should have received anthracycline- or paclitaxel-based chemotherapy prior to the use of pyrrolitinib.
Key points for rational dosing:
1. HER2 status should be tested using a well-validated assay prior to treatment with pyrrolitinib. Pyrrolitinib should only be used in HER2-positive breast cancer patients.
2. For patients with HER2-positive recurrent or metastatic breast cancer.
3. Pivotal treatment with pyrrolitinib should be continued as long as clinical benefit is observed until the patient becomes intolerant or the disease progresses.
4. The recommended dose of pyrrolitinib is 400 mg orally once daily, within 30 minutes after a meal, at the same time each day. The dose should be taken continuously in cycles of 21 days. If a patient misses a day’s dose of pyrrolitinib, there is no need to make up the dose and the next dose will be taken as scheduled.
5. If patients experience adverse reactions during treatment, they can be managed by suspending dosing, reducing the dose, or stopping dosing. For diarrhea and skin adverse reactions, symptomatic treatment can be administered first and closely observed. Some persistent Grade 2 adverse reactions may also require multiple dose suspensions and/or dose reductions. If subjects continue to have clinically uncontrollable (i.e., persistent after ≤14 days of clinical treatment or observation with ≥two occurrences) adverse events after suspension of dosing, the dose should be reduced by one level when resuming dosing after suspension, with pyrrolizidine allowing a minimum dose downward adjustment of 240 mg.
6. In case of combined use of strong inhibitors of CYP3A4 and strong inducers, close monitoring should be performed and dose adjustment should be considered in conjunction with clinical observation.
7. Pyrrolitinib is mainly metabolized by the liver and is not recommended for patients with moderate to severe hepatic impairment. Renal impairment has a very limited effect on pyrrolitinib exposure. Patients with renal impairment should still use pyrrolitinib with caution under the guidance of a physician.
8. Diarrhea was the most common adverse reaction observed in clinical trials of pyrrolitinib. Patients should be concerned about changes in bowel movement properties and frequency during treatment and start antidiarrheal therapy with loperamide or montelukast as soon as possible after detection of unformed stools. In case of persistent grade 3 diarrhea, or grade 1 to 2 diarrhea with complications (≥ grade 2 nausea, vomiting, fever, blood in stool, or dehydration), patients should contact their physician immediately and receive therapeutic instructions to start symptomatic treatment as soon as possible. Diarrhea may be managed according to dose adjustment guidelines after its occurrence. Patients who experience frequent diarrhea during treatment should be alerted to the possibility of severe diarrhea.
9. Safety and efficacy data for pyrrolitinib in pediatric and adolescent patients under 18 years of age are lacking.
10. Data from the phase III clinical trial of pyrrolitinib (PUFFIN) showed that pyrrolitinib in combination with capecitabine significantly prolonged median progression-free survival compared with lapatinib in combination with capecitabine in patients with HER2-positive metastatic breast cancer who had failed prior trastuzumab therapy and received concomitant anthracycline- or paclitaxel-based chemotherapy (12.5 months vs 6.8 months, HR = 0.39, p <0.0001).