title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: Instituto de Investigaciones Biomédicas de Sevilla, Hospital Universitario Virgen del Rocío/Universidad de Sevilla/CSIC, Seville, Spain. Electronic address: lpazaresr@seom.org.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.affiliation: Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Pulmonary Oncological First Unit, Azienda Ospedaliera S. Camillo Forlanini, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Marinis
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University Cancer Center, Stanford, California.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Department of Clinical & Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.affiliation: Department of Pulmonology XIV, Koranyi National Institute of TB and Pulmonology I and XIV, Budapest, Hungary.
authors.forename: Erszébet
authors.initials: E
authors.lastname: Juhász
authors.affiliation: Unidad de Oncologia Tocacica, International Center of Clinical Studies, Santiago, Chile.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Arén
authors.affiliation: Cancer Hospital/Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmelter
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, New Jersey.
authors.forename: Teng Jin
authors.initials: TJ
authors.lastname: Ong
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, New Jersey.
authors.forename: Carol
authors.initials: C
authors.lastname: Peña
authors.affiliation: Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Tony S
authors.initials: TS
authors.lastname: Mok
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors / Q000235:genetics; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: EGFR mutation; KRAS mutation; Molecular targeted therapy; Non-small-cell lung cancer; Sorafenib