Single-center phase 2 trial of pyrotinib plus metronomic etoposide in heavily pretreated HER2-positive metastatic breast cancer

Pyrotinib is a novel pan-HER tyrosine kinase inhibitor with activity for HER2-positive metastatic breast cancer (mBC) in various phase 1-3 studies. Novel combinations of pyrotinib with other agents are being investigated. A phase 2 trial at the Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) evaluated the combination of pyrotinib with metronomic etoposide for heavily pretreated patients with HER2-positive mBC. Median number of prior treatment lines was 4 (range 2-7), including trastuzumab in all patients. Oral pyrotinib 400 mg once daily plus metronomic oral etoposide 50 mg per day on d1-d21 every 28 days resulted in median progression-free survival and overall survival of 9.0 months (95% CI 7.6-10.4) and 27.0 months (20.9-33.1), respectively. There were no grade 4 or 5 adverse events; the most common grade 3 adverse events were nausea (15% of patients), vomiting (15%) diarrhea (5%), anemia (5%), and peripheral neurpathy (5%). The authors conclude that the combination of pyrotinib with metronomic etoposide had promising activity among patients with heavily pretreated HER2-positive mBC, with acceptable toxicity.