Pyrotinib in combination with metronomic oral vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy: A single-center, single-arm, prospective phase 2 study.

Abstract

1033 Background: In 15% to 30% of breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed, this is related to aggressive disease and poor prognosis. Although important clinical benefits for patients have been achieved by the use of the HER2 antibody trastuzumab, 50% to 74% of patients with metastatic disease have no response to treatment, and approximately 75% progress within one year. The purpose of this study was to evaluate the efficacy and safety of oral pyrotinib in combination with oral metronomic vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. Methods: This prospective phase 2 study enrolled patients aged 18-75 years with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy, and had an Eastern Cooperative Oncology Group performance score of 0-2. Patients received pyrotinib 400 mg once daily and vinorelbine 40 mg once on Monday, Wednesday, Friday of each week until disease progression or unacceptable toxicity. Both pyrotinib and vinorelbine were orally administered 30 min after meals. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease remission rate (DCR), overall survival (OS), quality of life (QoL) and safety (CTCAE 5.0). The follow-up of this study is ongoing, but enrolment is closed. This study is registered on Clinical Trials.gov, number NCT04903652. Results: Between Oct 21, 2019, and Jan 21, 2022, 36 patients were enrolled and all of them were included in the intent-to-treat (ITT) population. 20 of 36 patients had disease progress or death. Median follow-up was 16.23 months. The median PFS (mPFS) was 14.23 months (95% CI 8.13-20.33). The ORR and DCR were 38.9% and 83.3%, respectively. The median OS was not reached. Grade 3 adverse events (AEs) occurred in 17 of 36 patients, the most common were diarrhea 27.8% and stomachache 5.6%. No grade 4 AEs were observed. Conclusions: Pyrotinib combined with metronomic oral vinorelbine showed promising efficacy and manageable safety in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. This study might represent a potential treatment option for these patients. Clinical trial information: NCT04903652..