Mary E R O'Brien1, Rabab Gaafar2, Baktiar Hasan3, Jessica Menis4, Tanja Cufer5, Sanjay Popat6, Penella J Woll7, Veerle Surmont8, Vassilis Georgoulias9, Ana Montes10, Fiona Blackhall11, Ivo Hennig12, Gerald Schmid-Bindert13, Paul Baas14. 1. Royal Marsden Hospital, London and Sutton, United Kingdom. Electronic address: mary.obrien@rmh.nhs.uk. 2. NCI, Cairo University, Egypt. Electronic address: rabab.gaafar@gmail.com. 3. EORTC Headquarters, Brussels, Belgium. Electronic address: Baktiar.hasan@eortc.be. 4. EORTC Headquarters, Brussels, Belgium. Electronic address: Jessica.menis@eortc.be. 5. University Clinic Golnik, Golnik, Slovenia. Electronic address: tanja.cufer@klinika-golnik.si. 6. Royal Marsden Hospital, London and Sutton, United Kingdom. Electronic address: sanjay.popat@rmh.nhs.uk. 7. University of Sheffield, Sheffield, United Kingdom. Electronic address: p.j.woll@sheffield.ac.uk. 8. Ghent University Hospital, Belgium. Electronic address: veerle.surmont@uzgent.be. 9. University General Hospital Heraklion, Greece. Electronic address: georgsec@med.uoc.gr. 10. Guy's and St. Thomas' NHS - Guy's Hospital, London, United Kingdom. Electronic address: ana.montes@gstt.nhs.uk. 11. The Christie Hospital NHS Foundation, Manchester, United Kingdom. Electronic address: Fiona.Blackhall@christie.nhs.uk. 12. Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom. Electronic address: ivo.hennig@nuh.nhs.uk. 13. Universitaetsmedizin Mannheim, Mannheim, Germany. Electronic address: gerald.schmid-bindert@umm.de. 14. The Netherlands Cancer Institute - Antoni Van LeeuweenhoekZiekenhuis, Amsterdam, The Netherlands. Electronic address: p.baas@nki.nl.
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 topazopanib (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.
RCT Entities:
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 NSCLCpatients had limited side-effects. This study was stopped due to lack of efficacy by stringent criteria for PFS at a futility interim analysis.