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Clinical Trial
. 2012 Oct;7(10):1574-82.
doi: 10.1097/JTO.0b013e31826149ba.

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  1 , Ju-Whei Lee, Nasser H Hanna, Anne M Traynor, David P Carbone, Joan H Schiller
Affiliations
Clinical Trial

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 et al. J Thorac Oncol. 2012 Oct.

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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Figures

Figure 1
Figure 1
Schema of study steps
Figure 2
Figure 2
Consort Diagram
Figure 3
Figure 3
Progression-Free Survival by Step of Study, (a) step 1, (b) step 2, (c) step 3
Figure 3
Figure 3
Progression-Free Survival by Step of Study, (a) step 1, (b) step 2, (c) step 3
Figure 3
Figure 3
Progression-Free Survival by Step of Study, (a) step 1, (b) step 2, (c) step 3
Figure 4
Figure 4
Overall Survival by Step of Study, (a) step 1, (b) step 2, (c) step 3
Figure 4
Figure 4
Overall Survival by Step of Study, (a) step 1, (b) step 2, (c) step 3
Figure 4
Figure 4
Overall Survival by Step of Study, (a) step 1, (b) step 2, (c) step 3
See this image and copyright information in PMC

References

    1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011 Jul-Aug;61(4):212–36. - PubMed
    1. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123–32. - PubMed
    1. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099–109. - PubMed
    1. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003 Jan;3(1):11–22. - PubMed
    1. Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM, et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 2006 Mar 1;98(5):326–34. - PubMed

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