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, James Moon, Mary Redman, Shirish M. Gadgeel, Karen Kelly, Philip C. Mack, Hanna M. Saba, Mohamed K. Mohamed, Mohammad Jahanzeb, David R. Gandara

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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/m2 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.

Original languageEnglish
Pages (from-to)2463-2470
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number23
DOIs
StatePublished - Aug 10 2014

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Topotecan
Small Cell Lung Carcinoma
Platinum
Disease-Free Survival
Survival
aflibercept
Disease Susceptibility
Blood Vessels
Therapeutics
Hemorrhage
Neoplasm Metastasis
Drug Therapy
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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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. / Allen, Jeffrey W.; Moon, James; Redman, Mary; Gadgeel, Shirish M.; Kelly, Karen; Mack, Philip C.; Saba, Hanna M.; Mohamed, Mohamed K.; Jahanzeb, Mohammad; Gandara, David R.

In: Journal of Clinical Oncology, Vol. 32, No. 23, 10.08.2014, p. 2463-2470.

Research output: Contribution to journalArticle

Allen, Jeffrey W. ; Moon, James ; Redman, Mary ; Gadgeel, Shirish M. ; Kelly, Karen ; Mack, Philip C. ; Saba, Hanna M. ; Mohamed, Mohamed K. ; Jahanzeb, Mohammad ; Gandara, David R. / 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. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 23. pp. 2463-2470.
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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/m2 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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T2 - A randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer

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AU - Moon, James

AU - Redman, Mary

AU - Gadgeel, Shirish M.

AU - Kelly, Karen

AU - Mack, Philip C.

AU - Saba, Hanna M.

AU - Mohamed, Mohamed K.

AU - Jahanzeb, Mohammad

AU - Gandara, David R.

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