Eribulin plus pyrotinib In trastuzumab-resistant HER2-positive advanced breast cancer: A single-arm, multicenter phase II trial (EPIC trial).

Abstract

1031 Background: This study (ChiCTR2000038832) aimed to evaluate the efficacy and safety of combining eribulin with pyrotinib in patients with advanced HER2-positive breast cancer who had developed resistance to trastuzumab. These patients typically face a poor clinical prognosis, and evidence-based guidance for treatment decisions remains limited. Methods: Eligible patients were those with pathologically confirmed HER2-positive metastatic breast cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and prior treatment with trastuzumab and taxanes. Participants received oral pyrotinib (400 mg once daily) and intravenous eribulin (1.4 mg/m² on days 1 and 8 of each 21-day cycle) for up to six cycles. Pyrotinib was continued until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints include the objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety. Results: Between February 2021 and September 2023, 30 patients were enrolled, with a median age of 57 years (range: 30–76). All had received prior trastuzumab and taxane therapies. As of November 30, 2024, the median follow-up was 20.1 months. Disease progression or death occurred in 15 patients, and the median PFS was 13.73 months (95% confidence interval [CI]: 11.1–14.8). The 12-month PFS rate was 61.7% (95% CI: 44.2%–86.0%). The 12-month OS rate was 75.3% (95% CI: 66.2%–84.4%). The objective response rate (ORR) was 53.3% (16/30), and the disease control rate (DCR) was 80.0% (24/30). Median overall survival was not reached. Common adverse events (AEs) of any grade occurring in > 15% of patients included diarrhea (40%), nausea (20%), anorexia (16%), and vomiting (16%), with grade 3 diarrhea reported in 3% of patients. No treatment-related deaths were observed. Conclusions: The combination of eribulin and pyrotinib shows promise as a therapeutic option for patients with HER2-positive advanced breast cancer resistant to trastuzumab. While advancements in anti-HER2 therapies continue, further studies are needed to address unresolved challenges in this clinical context. Clinical trial information: ChiCTR2000038832 .