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.
Author(s): Allen JW(1), Moon J(2), Redman M(2), Gadgeel SM(2), Kelly K(2), Mack PC(2), Saba
HM(2), Mohamed MK(2), Jahanzeb M(2), Gandara DR(2).
Affiliation(s): Author information:
(1)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. (2)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.
Publication date & source: 2014, J Clin Oncol. , 32(23):2463-70
PURPOSE: 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.
PATIENTS AND 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.
CONCLUSION: 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.
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