A double-blind randomized discontinuation phase-ii study of sorafenib (BAY 43-9006) in previously treated non-small-cell lung cancer patients: Eastern cooperative oncology group study E2501

Heather A. Wakelee, Ju Whei Lee, Nasser Hanna, Anne M. Traynor, David P. Carbone, Joan H. Schiller

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Introduction: Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase-II study in heavily pretreated non-small-cell lung cancer (NSCLC) patients (≥ 2 prior therapies) used a randomized discontinuation design. Methods: Patients received 400 mg of sorafenib orally twice daily for two cycles (2 months) (step 1). Responding patients on step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease 2 months after randomization. Results: There were 299 patients evaluated for step 1; of these, 81 eligible patients were randomized on step 2 and received sorafenib (n = 50) or placebo (n = 31). The 2-month disease control rates after randomization were 54% and 23% for patients initially receiving sorafenib and placebo, respectively, p = 0.005. The hazard ratio for progression on step 2 was 0.51 (95% [confidence interval] CI 0.30, 0.87, p = 0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), hazard ratio 0.67 (95% CI 0.40-1.11), p = 0.117. A dispensing error occurred, which resulted in the unblinding of some patients, but not before completion of the 8-week initial step 2 therapy. Toxicities were manageable and as expected. Conclusions: The results of this randomized discontinuation trial suggest that sorafenib has single-agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC.

Original languageEnglish
Pages (from-to)1574-1582
Number of pages9
JournalJournal of Thoracic Oncology
Volume7
Issue number10
DOIs
StatePublished - Oct 2012

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Non-Small Cell Lung Carcinoma
Random Allocation
Placebos
sorafenib
raf Kinases
Angiogenesis Inhibitors
Confidence Intervals
Survival

Keywords

  • Non-small-cell lung cancer
  • Randomized discontinuation trial
  • Sorafenib

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

A double-blind randomized discontinuation phase-ii study of sorafenib (BAY 43-9006) in previously treated non-small-cell lung cancer patients : Eastern cooperative oncology group study E2501. / Wakelee, Heather A.; Lee, Ju Whei; Hanna, Nasser; Traynor, Anne M.; Carbone, David P.; Schiller, Joan H.

In: Journal of Thoracic Oncology, Vol. 7, No. 10, 10.2012, p. 1574-1582.

Research output: Contribution to journalArticle

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abstract = "Introduction: Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase-II study in heavily pretreated non-small-cell lung cancer (NSCLC) patients (≥ 2 prior therapies) used a randomized discontinuation design. Methods: Patients received 400 mg of sorafenib orally twice daily for two cycles (2 months) (step 1). Responding patients on step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease 2 months after randomization. Results: There were 299 patients evaluated for step 1; of these, 81 eligible patients were randomized on step 2 and received sorafenib (n = 50) or placebo (n = 31). The 2-month disease control rates after randomization were 54{\%} and 23{\%} for patients initially receiving sorafenib and placebo, respectively, p = 0.005. The hazard ratio for progression on step 2 was 0.51 (95{\%} [confidence interval] CI 0.30, 0.87, p = 0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), hazard ratio 0.67 (95{\%} CI 0.40-1.11), p = 0.117. A dispensing error occurred, which resulted in the unblinding of some patients, but not before completion of the 8-week initial step 2 therapy. Toxicities were manageable and as expected. Conclusions: The results of this randomized discontinuation trial suggest that sorafenib has single-agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC.",
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AU - Lee, Ju Whei

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AU - Schiller, Joan H.

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