Trabectedin as a single-agent treatment of advanced breast cancer after anthracycline and taxane treatment: a multicenter, randomized, phase II study comparing 2 administration regimens

Clin Breast Cancer. 2014 Dec;14(6):396-404. doi: 10.1016/j.clbc.2014.06.006. Epub 2014 Aug 15.

Abstract

Background: The purpose of this study was to assess the efficacy and safety of trabectedin for advanced breast cancer.

Patients and methods: In an open-label, phase II, multicenter study, women with advanced breast cancer previously treated with ≤ 2 lines of chemotherapy for advanced disease, including both anthracyclines and taxanes, were randomized (1:1) to 3-hour infusions of trabectedin 1.3 mg/m(2) once every 3 weeks (1/3 treatment arm) or 0.58 mg/m(2) every week for 3 of 4 weeks (3/4 treatment arm). The primary end point was objective response. Secondary end points included time to progression (TTP), progression-free survival (PFS), and overall survival (OS).

Results: Fifty-two women (median age, 50 years; median chemotherapy agents, 4) were enrolled. Relative trabectedin dose intensities were 81% and 76% in the 1/3 and 3/4 treatment arms, respectively. Objective response rates were 12% (3 of 25) and 4% (1 of 27), respectively. Stable disease was observed in 14 (56%) and 11 (41%) patients in the 1/3 and 3/4 treatment arms, respectively, with median durations of 3.5 and 3.7 months. Median TTP and PFS were higher in the 1/3 treatment arm (3.1 months each) than in the 3/4 treatment arm (2.0 months each). At a median follow-up of 7 months in both treatment arms, median OS was not reached in the 1/3 treatment arm and was 9.4 months in the 3/4 treatment arm. The most frequent drug-related adverse events in the 1/3 and 3/4 treatment arms, respectively, were alanine aminotransferase (ALT) level increases (68% vs. 63%), nausea (56% vs. 59%), and asthenia (56% vs. 48%). Neutropenia and increases in ALT levels were the most frequent grade 3/4 events. Both types of events were usually transient and reversible.

Conclusion: In the population studied, trabectedin showed a manageable safety profile for both regimens analyzed. There were higher objective response rates and a longer PFS in the 1/3 treatment arm compared with the 3/4 treatment arm.

Trial registration: ClinicalTrials.gov NCT00050427.

Keywords: Ecteinascidin-743; Objective response rate; Overall survival; Progression-free survival; Safety; Time to progression.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / drug therapy*
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology
  • Dioxoles / administration & dosage
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Salvage Therapy*
  • Survival Rate
  • Taxoids / administration & dosage
  • Tetrahydroisoquinolines / administration & dosage
  • Trabectedin
  • Young Adult

Substances

  • Anthracyclines
  • Dioxoles
  • Taxoids
  • Tetrahydroisoquinolines
  • Trabectedin

Associated data

  • ClinicalTrials.gov/NCT00050427