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

• Published in: Journal of thoracic oncology 2012-10, Vol.7 (10), p.1574-1582
• Main Authors: Wakelee, Heather A., Lee, Ju-Whei, Hanna, Nasser H., Traynor, Anne M., Carbone, David P., Schiller, Joan H.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma, Bronchiolo-Alveolar - drug therapy; Adenocarcinoma, Bronchiolo-Alveolar - mortality; Adenocarcinoma, Bronchiolo-Alveolar - pathology; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Benzenesulfonates - therapeutic use; Carcinoma, Large Cell - drug therapy; Carcinoma, Large Cell - mortality; Carcinoma, Large Cell - pathology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Niacinamide - analogs & derivatives; Non–small-cell lung cancer; Phenylurea Compounds; Prognosis; Pyridines - therapeutic use; Randomized discontinuation trial; Salvage Therapy; Sorafenib; Survival Rate
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0b013e31826149ba

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. 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. 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. 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.