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Clinical Trial
. 2014 Aug 10;32(23):2463-70.
doi: 10.1200/JCO.2013.51.4109. Epub 2014 Jul 7.

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

Jeffrey W Allen  1 , James Moon  2 , Mary Redman  2 , Shirish M Gadgeel  2 , Karen Kelly  2 , Philip C Mack  2 , Hanna M Saba  2 , Mohamed K Mohamed  2 , Mohammad Jahanzeb  2 , David R Gandara  2
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Clinical Trial

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

Jeffrey W Allen et al. J Clin Oncol. .

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00828139.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram.
Fig 2.
Fig 2.
Comparison of treatment arms within subgroups: progression-free survival for patients with (A) platinum-sensitive disease and (B) platinum-refractory disease; overall survival for patients with (C) platinum-sensitive disease and (D) platinum-refractory disease.
See this image and copyright information in PMC

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