title: 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: BACKGROUND
  New treatment options are needed for second-line therapy in patients with NSCLC.
  
  
  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).
  
  
  CONCLUSIONS
  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.affiliation: Universitätsklinikum Freiburg, Department of Internal Medicine, Oncology, Hematology, and Stem Cell Transplantation, Freiburg, Germany. Electronic address: Cornelius.waller@uniklinik-freiburg.de.
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Waller
authors.affiliation: Sumy State University, Sumy Regional Clinical Oncological Dispensary Thoracic Department, Sumy, Ukraine.
authors.forename: Ihor
authors.initials: I
authors.lastname: Vynnychenko
authors.affiliation: Municipal Multifield Clinical Hospital #4, Department of Chemotherapy, Donetsk State Medical University, Donetsk, Ukraine.
authors.forename: Igor
authors.initials: I
authors.lastname: Bondarenko
authors.affiliation: Department of Chemotherapy, Lviv State Oncology Regional Treatment and Diagnostic Center, Lviv, Ukraine.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Shparyk
authors.affiliation: Quintiles, Durham, NC.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Hodge
authors.affiliation: Quintiles, Durham, NC.
authors.forename: Anne
authors.initials: A
authors.lastname: Freeman
authors.affiliation: Quintiles, Durham, NC.
authors.forename: Brian
authors.initials: B
authors.lastname: Huber
authors.affiliation: Quintiles, Durham, NC.
authors.forename: Ronald
authors.initials: R
authors.lastname: Lieberman
authors.affiliation: Quintiles, Durham, NC.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shelton
authors.affiliation: Quintiles, Durham, NC.
authors.forename: Harish
authors.initials: H
authors.lastname: Dave
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005663:Furans / Q000008:administration & dosage; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007659:Ketones / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000068437:Pemetrexed; D015996:Survival Rate; D016896:Treatment Outcome; D000095662:Polyether Polyketides
chemical_list: D000964:Antimetabolites, Antineoplastic; D005663:Furans; D005971:Glutamates; D006147:Guanine; D007659:Ketones; D000068437:Pemetrexed; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Eribulin mesylate; Overall survival; Phase II clinical trial; Progression-free survival; Time to progression