Batchelor 2013.

Study characteristics
Methods	A phase 3, 3‐arm, multicentre RCT with partial blinding; ratio 2:2:1 Country: Canada, Germany, France, the Netherlands, UK, USA Accrual dates: Oct 2008 to Sept 2009 Trial reg: NCT00777153, REGAL Funding: AstraZeneca DOI: several authors declared stock interests and pharmaceutical funding
Participants	No. randomised: 325 No. analysed: 323 Inclusion criteria: People with recurrent GBM after TMZ + RT (first recurrence); Karnofsky PS > 70%; MMSE > 15; life expectancy of > 12 weeks Exclusions: prior anti‐VEGF therapy or cranial radiation within 3 months of study entry Age: median age = 54 years Gender: NR KPS PS: 70 to 80 = 50% group 1, 48% group 2 and 36.2% group 3; 80 to 100 = 50% group 1, 51.2% group 2; 62.5% group 3 Resection for recurrent disease: group 1 = 38.2%, group 2 = 38%, group 3 = 36.9% MGMT: NR Initial treatment: TMZ + RT
Interventions	Arm 1: cediranib monotherapy (30 mg daily po) Arm 2: cediranib (20 mg daily po) + lomustine (110 mg po every 6 weeks) Arm 3: lomustine  (110 mg po every 6 weeks) + placebo (once daily)
Outcomes	PFS, OS, SAEs, TTD
Notes	Group 3 had better PS than the other groups.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Patients randomly assigned, stratified by age and resection status". Not specifically stated.
Allocation concealment (selection bias)	Unclear risk	Not reported.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo was identical to the cediranib.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"independent, centralized, treatment‐arm blinded radiographic review"
Incomplete outcome data (attrition bias) All outcomes	Low risk	2 patients excluded from analysis
Selective reporting (reporting bias)	Low risk	Expected outcomes reported.
Other bias	Unclear risk	Funding and author interests noted.