Abstract 239P
Background
Pyrotinib is a small molecule tyrosine kinase inhibitor targeting HER1, HER2, and HER4. The phase III PHOEBE trial has proved its superiority over lapatinib when in combination with capecitabine in previously treated, HER2-positive metastatic breast cancer. This phase II trial aimed to investigate the activity of pyrotinib plus docetaxel as first-line treatment in HER2-positive metastatic breast cancer.
Methods
Patients with measurable disease received oral pyrotinib 400 mg once daily until disease progression or intolerable toxicity. Intravenous docetaxel was given at 75 mg/m2 on day 1 for at least six 21-day cycles. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST 1.1. The study is registered with ClinicalTrials.gov, NCT03876587.
Results
Between June 2019 and June 2021, a total of 79 patients enrolled and received study treatment. The confirmed ORR in 79 patients was 77.2% (95% CI, 66.4%-85.9%); 3 patients achieved CR and 58 achieved PR. The confirmed ORR in the per-protocol set (n=79) was 79.2% (95% CI, 68.5%-87.6%) . As of April 30, 2022, a total of 75 patients achieved PFS events and 4 patient dropouts due to safety. Median follow-up duration was 17.38 months, median progression-free survival was 15.03 months (95% CI,10.54-19.53). Of 79 patients, the most common grade 3 or 4 treatment-emergent adverse events included decreased white blood cell count (23 [29.1%]), decreased neutrophil count (22 [27.8%]), diarrhea (17 [21.5%]), and hypokalemia (five [6.3%]) . Grade ≥3 diarrhea was less common in patients with loperamide prophylaxis (8.9%; 4/45) than in those without loperamide prophylaxis (38.2%; 13/34). Grade ≥3 decreased white blood cell count and/or decreased neutrophil count was less common in patients with granulocyte colony-stimulating factor (G-CSF) prophylaxis (23.3%; 10/43) than in those without G-CSF prophylaxis (36.1%; 13/36).
Conclusions
Pyrotinib in combination with docetaxel exhibits promising antitumor activity and acceptable safety profile among patients with HER2-positive metastatic breast cancer in the first-line setting. Loperamide prophylaxis is an effective approach for the prevention of diarrhea.
Clinical trial identification
NCT03876587 03/12/2019.
Editorial acknowledgement
Legal entity responsible for the study
Xiaojia Wang.
Funding
JIANGSU HENGRUI MEDICINE CO.,LTD.
Disclosure
All authors have declared no conflicts of interest.