PMID- 26074395 OWN - NLM STAT- MEDLINE DCOM- 20150921 LR - 20211203 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 51 IP - 12 DP - 2015 Aug TI - 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). PG - 1511-28 LID - S0959-8049(15)00388-3 [pii] LID - 10.1016/j.ejca.2015.04.026 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - O'Brien, Mary E R AU - O'Brien ME AD - Royal Marsden Hospital, London and Sutton, United Kingdom. Electronic address: mary.obrien@rmh.nhs.uk. FAU - Gaafar, Rabab AU - Gaafar R AD - NCI, Cairo University, Egypt. Electronic address: rabab.gaafar@gmail.com. FAU - Hasan, Baktiar AU - Hasan B AD - EORTC Headquarters, Brussels, Belgium. Electronic address: Baktiar.hasan@eortc.be. FAU - Menis, Jessica AU - Menis J AD - EORTC Headquarters, Brussels, Belgium. Electronic address: Jessica.menis@eortc.be. FAU - Cufer, Tanja AU - Cufer T AD - University Clinic Golnik, Golnik, Slovenia. Electronic address: tanja.cufer@klinika-golnik.si. FAU - Popat, Sanjay AU - Popat S AD - Royal Marsden Hospital, London and Sutton, United Kingdom. Electronic address: sanjay.popat@rmh.nhs.uk. FAU - Woll, Penella J AU - Woll PJ AD - University of Sheffield, Sheffield, United Kingdom. Electronic address: p.j.woll@sheffield.ac.uk. FAU - Surmont, Veerle AU - Surmont V AD - Ghent University Hospital, Belgium. Electronic address: veerle.surmont@uzgent.be. FAU - Georgoulias, Vassilis AU - Georgoulias V AD - University General Hospital Heraklion, Greece. Electronic address: georgsec@med.uoc.gr. FAU - Montes, Ana AU - Montes A AD - Guy's and St. Thomas' NHS - Guy's Hospital, London, United Kingdom. Electronic address: ana.montes@gstt.nhs.uk. FAU - Blackhall, Fiona AU - Blackhall F AD - The Christie Hospital NHS Foundation, Manchester, United Kingdom. Electronic address: Fiona.Blackhall@christie.nhs.uk. FAU - Hennig, Ivo AU - Hennig I AD - Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom. Electronic address: ivo.hennig@nuh.nhs.uk. FAU - Schmid-Bindert, Gerald AU - Schmid-Bindert G AD - Universitaetsmedizin Mannheim, Mannheim, Germany. Electronic address: gerald.schmid-bindert@umm.de. FAU - Baas, Paul AU - Baas P AD - The Netherlands Cancer Institute - Antoni Van LeeuweenhoekZiekenhuis, Amsterdam, The Netherlands. Electronic address: p.baas@nki.nl. CN - EORTC-LCG LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150611 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Indazoles) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - 7RN5DR86CK (pazopanib) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Disease Progression MH - Disease-Free Survival MH - Double-Blind Method MH - Female MH - Humans MH - Indazoles MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy MH - Maintenance Chemotherapy/*methods MH - Male MH - Middle Aged MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Pyrimidines/adverse effects/*therapeutic use MH - Sulfonamides/adverse effects/*therapeutic use OTO - NOTNLM OT - Advanced OT - Double blind OT - Maintenance OT - NSCLC OT - Pazopanib OT - Phase III EDAT- 2015/06/16 06:00 MHDA- 2015/09/22 06:00 CRDT- 2015/06/16 06:00 PHST- 2015/04/28 00:00 [received] PHST- 2015/04/30 00:00 [accepted] PHST- 2015/06/16 06:00 [entrez] PHST- 2015/06/16 06:00 [pubmed] PHST- 2015/09/22 06:00 [medline] AID - S0959-8049(15)00388-3 [pii] AID - 10.1016/j.ejca.2015.04.026 [doi] PST - ppublish SO - Eur J Cancer. 2015 Aug;51(12):1511-28. doi: 10.1016/j.ejca.2015.04.026. Epub 2015 Jun 11.