First report of eribulin in combination with pertuzumab and trastuzumab for advanced HER2-positive breast cancer

Breast. 2017 Oct:35:78-84. doi: 10.1016/j.breast.2017.06.015. Epub 2017 Jun 27.

Abstract

Background: The efficacy and safety of continuing multiple anti-HER2 therapies in advanced breast cancer (ABC) patients remains unclear. This study investigated eribulin in combination with pertuzumab and trastuzumab for both taxane- and trastuzumab-pretreated HER2-positive ABC patients.

Methods: In a single-institute, single-arm, open-label, phase II trial, HER2-positive ABC patients who had previously received taxanes and trastuzumab were treated with eribulin in combination with pertuzumab and trastuzumab. The pharmacokinetics of eribulin in this combination were assessed in 6 patients. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary endpoint was objective response rate (ORR).

Results: A total of 30 patients (median age, 58 years; range, 31-76) were enrolled, with a median number of previous chemotherapy regimens of 3.5 (range: 1-9) in the metastatic setting. Pharmacokinetic parameters of eribulin in this combination were similar to previous reports of eribulin monotherapy. ORR was 34.8% (95% CI: 16.4-57.3, n = 23), and median progression-free survival was 42.6 weeks (95% CI: 20.3-51.9, n = 30). Clinical benefit rate was 60.9% (95% CI: 16.4-57.3). The most common grade 3/4 adverse event was neutropenia in 20 patients (66.7%). A dose reduction of eribulin was required in 27 patients due to adverse events, particularly grade 3 neutropenia.

Conclusions: Eribulin in combination with pertuzumab and trastuzumab was well tolerated in heavily pretreated patients. Eribulin may be a viable treatment option when used in combination with pertuzumab and trastuzumab for HER2-positive ABC patients (UMIN Clinical Trial Registry identification number, UMIN000012375).

Keywords: Eribulin; HER2-positive advanced breast cancer; Non-taxane microtubule dynamic inhibitor; Pertuzumab; Trastuzumab.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Furans / administration & dosage*
  • Humans
  • Ketones / administration & dosage*
  • Middle Aged
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab / administration & dosage*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Furans
  • Ketones
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • pertuzumab
  • eribulin
  • Trastuzumab