title: Southwest Oncology Group S0802: a randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer.
abstract: OBJECTIVE
  Development of new therapies for previously treated small-cell lung cancer (SCLC) is a major unmet need. Here, we describe a randomized, phase II trial of weekly topotecan with or without ziv-aflibercept (VEGF-trap) in this clinical setting.
  
  
  METHODS
  Patients with previously treated SCLC (one line of platinum-based chemotherapy), performance status of 0 to 1, adequate organ function, treated brain metastases, and no recent vascular events or bleeding diatheses were eligible. Eligible patients were stratified as platinum-sensitive or platinum-refractory and randomly assigned to receive weekly topotecan 4 mg/m(2) intravenously (IV) with or without ziv-aflibercept 6 mg/kg IV every 21 days. Progression-free survival (PFS) at 3 months was the primary end point.
  
  
  RESULTS
  In 189 randomly assigned patients, treatment arms were well balanced with regard to clinical characteristics. The 3-month PFS was significantly improved with the addition of ziv-aflibercept in patients who had platinum-refractory disease (27% v 10%; P = .02) but not in patients with platinum-sensitive disease (24% v 15%; P = .22). Although response rate was low, disease control rate was higher with combination therapy than with topotecan alone in patients who had platinum-sensitive disease (37% v 18%; P = .05) and in those who had platinum-refractory disease (25% v 15%; P = .14). Overall survival (OS) was not significantly improved in either strata. Grades 3 to 5 toxicities were more common with the addition of ziv-aflibercept.
  
  
  CONCLUSIONS
  Ziv-aflibercept improved the 3-month PFS in patients who had platinum-refractory SCLC, but its addition increased toxicity. OS was similar with combined ziv-aflibercept and topotecan compared with topotecan in both strata.
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL. Jeffrey.allen@stjoe.org.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Allen
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: Mary
authors.initials: M
authors.lastname: Redman
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: Shirish M
authors.initials: SM
authors.lastname: Gadgeel
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Saba
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Mohamed
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jahanzeb
authors.affiliation: Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D011993:Recombinant Fusion Proteins; D059004:Topoisomerase I Inhibitors; C533178:aflibercept; D019772:Topotecan; D040262:Receptors, Vascular Endothelial Growth Factor