title: Maintenance pazopanib versus placebo in Non-Small Cell Lung Cancer patients non-progressive after first line chemotherapy: A double blind randomised phase III study of the lung cancer group, EORTC 08092 (EudraCT: 2010-018566-23, NCT01208064).
abstract: BACKGROUND
  Switch maintenance is an effective strategy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Pazopanib is an oral, multi-targeted tyrosine kinase inhibitor (TKI). EORTC 08092 evaluated pazopanib given as maintenance treatment following standard first line platinum-based chemotherapy in patients with advanced NSCLC.
  
  
  METHODS
  Patients with non-progressive disease after 4-6 cycles of chemotherapy were randomised to receive either pazopanib 800mg/day or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival and secondary end-points were progression-free survival (PFS) and safety.
  
  
  RESULTS
  A total of 600 patients were planned to be randomised. The trial was prematurely stopped following an early interim analysis, after 102 patients were randomised to pazopanib (n=50) or placebo (n=52). Median age was 64years in both arms. Median overall survival was 17.4 months for pazopanib and 12.3 months for placebo (adjusted hazard ratio (HR) 0.72 [95% confidence interval (CI) 0.40-1.28]; p=0.257). Median PFS was 4.3 months versus 3.2 months (HR 0.67, [95% CI 0.43-1.03], p=0.068). PFS rates at 4 months were 56% and 45% respectively. The majority of treatment-related adverse events (AEs) were grade 1-2. Grade 3-4 AEs (pazopanib versus placebo) were hypertension (38% versus 8%), neutropenia (8% versus 0%), and elevated SGPT (6% versus 0%). Of the patients randomised to pazopanib, 22% withdrew due to a treatment-related AE.
  
  
  CONCLUSIONS
  Switch maintenance with pazopanib following platinum-based chemotherapy in advanced NSCLC patients had limited side-effects. This study was stopped due to lack of efficacy by stringent criteria for PFS at a futility interim analysis.
authors.affiliation: Royal Marsden Hospital, London and Sutton, United Kingdom. Electronic address: mary.obrien@rmh.nhs.uk.
authors.forename: Mary E R
authors.initials: ME
authors.lastname: O'Brien
authors.affiliation: NCI, Cairo University, Egypt. Electronic address: rabab.gaafar@gmail.com.
authors.forename: Rabab
authors.initials: R
authors.lastname: Gaafar
authors.affiliation: EORTC Headquarters, Brussels, Belgium. Electronic address: Baktiar.hasan@eortc.be.
authors.forename: Baktiar
authors.initials: B
authors.lastname: Hasan
authors.affiliation: EORTC Headquarters, Brussels, Belgium. Electronic address: Jessica.menis@eortc.be.
authors.forename: Jessica
authors.initials: J
authors.lastname: Menis
authors.affiliation: University Clinic Golnik, Golnik, Slovenia. Electronic address: tanja.cufer@klinika-golnik.si.
authors.forename: Tanja
authors.initials: T
authors.lastname: Cufer
authors.affiliation: Royal Marsden Hospital, London and Sutton, United Kingdom. Electronic address: sanjay.popat@rmh.nhs.uk.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Popat
authors.affiliation: University of Sheffield, Sheffield, United Kingdom. Electronic address: p.j.woll@sheffield.ac.uk.
authors.forename: Penella J
authors.initials: PJ
authors.lastname: Woll
authors.affiliation: Ghent University Hospital, Belgium. Electronic address: veerle.surmont@uzgent.be.
authors.forename: Veerle
authors.initials: V
authors.lastname: Surmont
authors.affiliation: University General Hospital Heraklion, Greece. Electronic address: georgsec@med.uoc.gr.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Guy's and St. Thomas' NHS - Guy's Hospital, London, United Kingdom. Electronic address: ana.montes@gstt.nhs.uk.
authors.forename: Ana
authors.initials: A
authors.lastname: Montes
authors.affiliation: The Christie Hospital NHS Foundation, Manchester, United Kingdom. Electronic address: Fiona.Blackhall@christie.nhs.uk.
authors.forename: Fiona
authors.initials: F
authors.lastname: Blackhall
authors.affiliation: Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom. Electronic address: ivo.hennig@nuh.nhs.uk.
authors.forename: Ivo
authors.initials: I
authors.lastname: Hennig
authors.affiliation: Universitaetsmedizin Mannheim, Mannheim, Germany. Electronic address: gerald.schmid-bindert@umm.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schmid-Bindert
authors.affiliation: The Netherlands Cancer Institute - Antoni Van LeeuweenhoekZiekenhuis, Amsterdam, The Netherlands. Electronic address: p.baas@nki.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007191:Indazoles; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy*; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: Advanced; Double blind; Maintenance; NSCLC; Pazopanib; Phase III