TY - JOUR
T1 - A double-blind randomized discontinuation phase-ii study of sorafenib (BAY 43-9006) in previously treated non-small-cell lung cancer patients
T2 - Eastern cooperative oncology group study E2501
AU - Wakelee, Heather A.
AU - Lee, Ju Whei
AU - Hanna, Nasser H.
AU - Traynor, Anne M.
AU - Carbone, David P.
AU - Schiller, Joan H.
N1 - Funding Information:
This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA49883, CA21076, and CA49957 and grants from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Non-small-cell lung cancer
KW - Randomized discontinuation trial
KW - Sorafenib
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UR - http://www.scopus.com/inward/citedby.url?scp=84866625336&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e31826149ba
DO - 10.1097/JTO.0b013e31826149ba
M3 - Article
C2 - 22982658
AN - SCOPUS:84866625336
SN - 1556-0864
VL - 7
SP - 1574
EP - 1582
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 10
ER -