Monotherapy Administration of Sorafenib in Patients with Non-Small Cell Lung Cancer (MISSION) Trial: A Phase III, Multicenter, Placebo-Controlled Trial of Sorafenib in Patients with Relapsed or Refractory Predominantly Nonsquamous Non-Small-Cell Lung Cancer after 2 or 3 Previous Treatment Regimens
Journal
Journal of Thoracic Oncology
Journal Volume
10
Journal Issue
12
Pages
1745-1753
Date Issued
2015
Author(s)
Paz-Ares L
Hirsh V
Zhang L
De Marinis F
Wakelee H.A
Seto T
Wu Y.-L
Novello S
Juhász E
Arén O
Sun Y
Schmelter T
Ong T.J
Penã C
Smit E.F
Mok T.S.
Abstract
Introduction: Sorafenib monotherapy has shown benefits in phase II trials as third-/fourth-line treatment in patients with non-small-cell lung cancer (NSCLC). Methods: The phase III, multinational, double-blind, placebo-controlled Monotherapy admInistration of Sorafenib in patientS wIth nOn-small-cell luNg cancer (MISSION) trial randomized patients with advanced relapsed/refractory NSCLC, following two or three prior treatment regimens, to sorafenib 400 mg twice a day (n = 350) or matching placebo (n = 353) plus best supportive care. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS) and time to progression. Epidermal growth factor receptor and KRAS mutation status was analyzed in archival tumor and/or circulating tumor DNA from blood samples obtained during screening. Results: Median OS was similar in the sorafenib and placebo groups (8.2 versus 8.3 mo; hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.84-1.17; p = 0.47). Median PFS (2.8 versus 1.4 mo; HR, 0.61; 95% CI, 0.51-0.72; p < 0.0001), and time to progression (2.9 versus 1.4 mo; HR, 0.54; 95% CI, 0.45-0.65; p < 0.0001) were significantly greater with sorafenib than with placebo. Among the 89 patients with epidermal growth factor receptor mutations, OS (13.9 versus 6.5 mo; HR, 0.48; 95% CI, 0.30-0.76; p = 0.002) and PFS (2.7 versus 1.4 mo; HR, 0.27; 95% CI, 0.16-0.46; p < 0.001) were significantly higher with sorafenib than placebo. PFS was significantly longer with sorafenib than placebo in patients with either wild-type or mutated KRAS, but OS was similar. Common drug-related adverse events were rash/desquamation, diarrhea, and fatigue, consistent with the safety profile of sorafenib. Conclusions: Third-/fourth-line sorafenib therapy did not significantly increase OS in patients with relapsed/refractory NSCLC, despite significantly increasing PFS. ? 2015 by the International Association for the Study of Lung Cancer.
Subjects
EGFR mutation; KRAS mutation; Molecular targeted therapy; Non-small-cell lung cancer; Sorafenib
SDGs
Other Subjects
antimetabolite; biological marker; DNA; docetaxel; epidermal growth factor receptor; epidermal growth factor receptor kinase inhibitor; K ras protein; paclitaxel; placebo; sorafenib; antineoplastic agent; carbanilamide derivative; EGFR protein, human; epidermal growth factor receptor; KRAS protein, human; nicotinamide; protein kinase inhibitor; protein p21; sorafenib; abdominal pain; adult; advanced cancer; aged; alopecia; anorexia; Article; backache; bleeding; blood sampling; cancer chemotherapy; cancer growth; cancer recurrence; central nervous system ischemia; circulating tumor cell; constipation; controlled study; coughing; desquamation; diarrhea; double blind procedure; drug dose reduction; drug efficacy; drug induced disease; drug safety; drug withdrawal; dyspnea; fatigue; female; fever; hand foot syndrome; headache; heart infarction; heart muscle ischemia; human; infection; major clinical study; male; molecularly targeted therapy; monotherapy; mucosa inflammation; multicenter study; mutation; nausea; non small cell lung cancer; overall survival; patient care; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; rash; side effect; thorax pain; treatment duration; treatment response; vomiting; weight reduction; wild type; analogs and derivatives; antagonists and inhibitors; Carcinoma, Non-Small-Cell Lung; clinical trial; enzymology; genetics; Lung Neoplasms; middle aged; molecularly targeted therapy; pathology; treatment outcome; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Mutation; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Proto-Oncogene Proteins p21(ras); Receptor, Epidermal Growth Factor; Treatment Outcome
Publisher
Lippincott Williams and Wilkins
Type
journal article