2 Clarke Drive
Suite 100
Cranbury, NJ 08512
© 2025 MJH Life Sciences™ and OncLive - Clinical Oncology News, Cancer Expert Insights. All rights reserved.
Eribulin with pyrotinib was safe and active in patients with HER2-positive advanced breast cancer who were resistant to treatment with trastuzumab.
Eribulin in combination with pyrotinib was safe and active in patients with HER2-positive advanced breast cancer who were resistant to treatment with trastuzumab (Herceptin), according to data from the phase 2 EPIC trial (ChiCTR2000038832) published in Drug Design, Development and Therapy.1
At the April 14, 2025, data cutoff, with a median follow-up of 26 months, patients who received the combination (n = 30) achieved a median progression-free survival (PFS) of 13.47 months (95% CI, 8.17-16.27) and a 12-month PFS rate of 61.7% (95% CI, 44.2%-86.0%). The objective response rate (ORR) was 56.7%. The median overall survival (OS) was not reached (NR); the 12-month OS rate was 75.3% (95% CI, 66.2%-84.4%).
“To our knowledge, this represents the first multicenter phase 2 trial investigating pyrotinib combined with eribulin in HER2-positive advanced breast cancer patients exhibiting primary trastuzumab resistance,” Ruoyang Li, MD, of the Breast Center at the Fourth Hospital of Hebei Medical University in Shijiazhuang, China, and coauthors wrote in the publication. “The eribulin-pyrotinib combination exhibited clinically meaningful efficacy in this extensively pretreated HER2-positive advanced breast cancer cohort. Furthermore, the combination demonstrated favorable tolerability without emergent safety signals, maintaining toxicity profiles consistent with individual agent monotherapies.”
EPIC was an investigator-initiated, multicenter study that enrolled female patients between the ages of 18 and 70 years with histologically confirmed HER2-positive advanced breast cancer.2 HER2 positivity was defined as an immunohistochemistry of 3+ and/or a fluorescence in situ hybridization ratio of at least 2.0. Patients were also required to have experienced documented disease progression following prior taxane chemotherapy and trastuzumab-based therapy.
Eligible patients received oral pyrotinib at 400 mg once daily in combination with intravenous eribulin at 1.4 mg/m2 on days 1 and 8 of each 28-day cycle. The combination was administered for 6 consecutive cycles; pyrotinib monotherapy continued beyond cycle 6 until disease progression, unacceptable toxicity, or patient withdrawal.
The primary end point was PFS. Secondary end points included ORR, OS, disease control rate (DCR), duration of response (DOR), and safety.
At baseline, the median age was 57 years (range, 30-76). Most patients were less than 65 years old (73.3%), had visceral metastatic sites at screening (86.7%), had estrogen receptor– or progesterone receptor–positive disease (70.0%), had an ECOG performance status of 0 (93.3%), had received trastuzumab for the treatment of advanced disease (53.3%), had not received prior capecitabine (70.0%), and had received 2 prior lines of therapy (80%).
The safety profile of eribulin plus pyrotinib was consistent with that of the individual agents.1 Any-grade treatment-emergent adverse effects (TEAEs) were reported in 90.0% of patients, including grade 3 or higher TEAEs in 33.3%. The most common grade 1 to 2 TEAEs included neutropenia (73.3%), diarrhea (70%), nausea/vomiting (66.7%), and peripheral neuropathy (63.3%). Grade 3 or 4 TEAEs consisted of neutropenia (16.7%), increased aspartate aminotransferase/alanine aminotransferase levels (13.3%), peripheral neuropathy (10%), nausea/vomiting (6.7%), anemia (3.3%), and diarrhea (3.3%).
Dose modifications (23.3%) and permanent treatment discontinuation (6.7%) were both reported. One patient withdrew from treatment due to intolerable symptoms. No instances of treatment-related mortality occurred.
Additional findings from EPIC demonstrated that the median DOR was 23.03 months (95% CI 21.7-NR); the maximum DOR exceeded 34 months. The DCR was 80.0% and the clinical benefit rate was 73.3%. Data from a prespecified subgroup analysis revealed that the treatment effects were consistent irrespective of prior capecitabine therapy (HR, 1.02, 95% CI 0.42-2.48; P = .5641).
“The combination regimen of eribulin and pyrotinib demonstrated a safe and feasible option for second-line treatment in patients with HER2-positive advanced breast cancer,” “Notably, clinical benefit persists in the capecitabine pretreated population. However, the current evidence is limited to Phase II clinical trial data, necessitating further validation through expanded sample sizes and controlled studies.
References
Related Content:
