Monotherapy Administration of Sorafenib in Patients with Non-Small Cell Lung Cancer: Phase III, Randomized, Double-Blind, Placebo-Controlled Mission Trial
Authors: L. Paz-Ares, V. Hirsh, L. Zhang, F. De Marinis, J.C-H. Yang, H. Wakelee, T. Seto, T. Schmelter, T.J. Ong, T.S.K. Mok, E.F. Smit
Journal: Annals of Oncology (2012)

ABSTRACT   Background  Sorafenib monotherapy showed activity in a randomized discontinuation phase II trial of patients with advanced NSCLC who failed 2–3 chemotherapy regimens (ECOG 2501). The Phase III MISSION trial assessed whether 3rd- or 4th-line treatment with sorafenib plus best supportive care (BSC) would improve overall survival (OS), relative to placebo plus BSC, in patients with advanced relapsed/refractory NSCLC of predominantly non-squamous histology.    Methods  Eligible patients were randomized 1:1 to oral sorafenib (S) 400 mg bid or placebo (P) and stratified by geographic region, number of prior lines of treatment, brain metastases, and prior anti-EGFR therapy. The primary endpoint was OS; secondary endpoints included progression free survival (PFS), time to progression (TTP), overall response rate (ORR), disease control rate (DCR), and safety; endpoints were tested with one-sided significance level of 0.025.    Results  A total of 703 patients were randomized (S = 350; P = 353). Baseline demographic factors and prior treatments were generally balanced, with minor imbalances (S vs P) in female gender (47% vs 41%) and never smokers (46% vs 38%). Fewer patients received post-progression therapy in the S arm (44%) than in the P arm (56%). Assessment of OS was based on a total of 579 events (S = 285, P = 294). Median OS was similar in the two groups (248 vs 253 d; HR 0.99, p = 0.4687), whereas median PFS (84 vs 43 d; HR 0.61; p     Conclusion  The phase III MISSION trial did not meet its primary endpoint of improving OS as 3rd- or 4th-line treatment in patients with advanced NSCLC. Sorafenib treatment significantly enhanced PFS, TTP, ORR, and DCR compared to BSC alone. Safety and tolerability data were as expected. Supported by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals.    Disclosure  L. Paz-Ares: Luis Paz-Ares has received honoraria from Bayer HealthCare Pharmaceuticals, Lilly, Roche and Pfizer  V. Hirsh: Member of the steering committee for the MISSION trial.  L. Zhang: Dr. Zhang has received research support from Bayer, Aventis, AstraZeneca, Henrui Pharm and Eli Lilly and has received consulting and lecture fees from Roche, Aventis, AstraZeneca and Eli Lilly.  J.C. Yang: Dr. Yang has acted in an advisory capacity for and received honoraria from Bayer Healthcare  H. Wakelee: Dr. Wakelee has received research funding from Bayer Healthcare  T. Seto: Dr. Seto has received research funding from Bayer Healthcare  T. Schmelter: Dr. Schmelter is an employee of Bayer HealthCare and owns stock in the corporation.  T.J. Ong: Dr. Ong is an employee of Bayer HealthCare and owns stock in the corporation.  T.S.K. Mok: Dr. Mok has received honoraria from AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, BeiGene, AVEO, Pfizer, Taiho, Boehringer Ingelheim, GSK Biologicals. He speaks for Astrazeneca, Roche, Eli Lilly, Boehringer Ingelheim, Merck Serono, and received research funding from Astrazeneca.  All other authors have declared no conflicts of interest.