An open-label, multicenter, randomized phase Ib/II study of eribulin mesylate administered in combination with pemetrexed versus pemetrexed alone as second-line therapy in patients with advanced nonsquamous non-small-cell lung cancer.

Abstract

INTRODUCTION:

New treatment options are needed for second-line therapy in patients with NSCLC.

PATIENTS AND METHODS:

This was a phase Ib/II study in patients with nonsquamous NSCLC in whom 1 previous platinum-based chemotherapy regimen had failed. Fifteen patients were enrolled in a dose escalation of eribulin mesylate in combination with pemetrexed (E+P). In phase II (n = 80), E+P at the maximum tolerated dose was compared with P.

RESULTS:

In phase Ib, the maximum tolerated dose of E+P was defined as eribulin 0.9 mg/m(2) with pemetrexed (500 mg/m(2)) each on day 1 of a 21-day cycle. In phase II, adverse events were comparable between groups. PFS and OS were similar between treatment groups. Median PFS was 21.4 weeks for E+P (n = 26; 95% confidence interval [CI], 12.7-39.6) and 23.4 weeks for P (n = 29; 95% CI, 17.1-29.9), with a hazard ratio of 1.0 (95% CI, 0.6-1.7).

CONCLUSION:

During phase Ib, E+P was tolerated only at a markedly lower dosing intensity relative to the eribulin monotherapy regimen approved for breast cancer and used in phase II studies of NSCLC. At the selected phase II dosing regimen, E+P was generally safe and well tolerated but provided no therapeutic advantage for the second-line treatment of locally advanced or metastatic nonsquamous NSCLC.

• Authors: Cornelius F Waller, Ihor Vynnychenko, Igor Bondarenko, Yaroslav Shparyk, Jeffrey P Hodge, Anne Freeman, Brian Huber, Ronald Lieberman, Mark J Shelton, Harish Dave
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 16 Issue 2 Pg. 92-9 (Mar 2015) ISSN: 1938-0690 [Electronic] United States
• PMID: 25458558 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Furans
• Glutamates
• Ketones
• Pemetrexed
• Guanine
• eribulin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Female
• Furans (administration & dosage)
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Ketones (administration & dosage)
• Lung Neoplasms (drug therapy, pathology)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Pemetrexed
• Survival Rate
• Treatment Outcome