A phase II study of halichondrin B analog eribulin mesylate (E7389) in patients with advanced non-small cell lung cancer previously treated with a taxane: a California cancer consortium trial

J Thorac Oncol. 2012 Mar;7(3):574-8. doi: 10.1097/JTO.0b013e31823f43ca.

Abstract

Introduction: Eribulin mesylate (E7389) is an analog of halichondrin B with a unique mechanism of microtubule binding. The activity and toxicity of eribulin were assessed in patients with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane.

Methods: An open-label phase II study included patients with NSCLC previously treated with platinum and taxane-based therapy, with up to two prior cytotoxic regimens, given for metastatic disease or as adjuvant therapy. Patients were stratified by taxane-sensitivity: taxane-sensitive (TS, progression >90 days after taxane) or taxane-resistant (TR, progression ≤90 days after taxane). Patients received an intravenous infusion of eribulin at 1.4 mg/m on days 1 and 8 every 21 days. The primary end point was objective response rate and secondary end points included progression-free survival and overall survival.

Results: Sixty-six patients were accrued. The objective response rate was 5% with a median duration of response of 7.8 months. In the TS arm, 3 of 45 patients (7%) achieved a partial response and another 11 of 45 (24%) achieved stable disease for at least 3 months, whereas in the TR arm, no patients achieved a partial response and 4 of 21 (19%) achieved stable disease for at least 3 months. Median progression-free survival was 2.9 months in the TS subgroup and 1.2 months in the TR subgroup. The median overall survival was 12.6 months in the TS subgroup and 8.9 months in the TR subgroup. Toxicities were primarily hematologic; only two patients developed grade 3 neuropathy.

Conclusions: Eribulin mesylate is well tolerated and demonstrates activity in pretreated, TS NSCLC.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bridged-Ring Compounds / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / mortality
  • Ethers, Cyclic / chemistry
  • Female
  • Follow-Up Studies
  • Furans / therapeutic use*
  • Humans
  • Ketones / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Macrolides / chemistry
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Platinum / administration & dosage
  • Salvage Therapy
  • Survival Rate
  • Taxoids / administration & dosage
  • Treatment Outcome

Substances

  • Bridged-Ring Compounds
  • Ethers, Cyclic
  • Furans
  • Ketones
  • Macrolides
  • Taxoids
  • taxane
  • halichondrin B
  • Platinum
  • eribulin