Eichelberg 2015.

Study characteristics
Methods	Study type: multicentre RCT Phase: 3 Accrual period: February 2009 to December 2011 Blinding: open label study Strata: MSKCC risk category IMC: data not found Crossover: from first to second line after disease progression
Participants	Histology: all histologies Prior systemic therapy: treatment‐naïve Measurable disease: required Non‐metastatic %: combined data not found M/F: 274/91 Eligible PS: ECOG PS 1 or better Age median (range): 65 (39 to 84) Prior nephrectomy: 335 Prognostic strata: system, good/intermediate/poor risk: MSKCC; 153/202/2
Interventions	sorafenib 400 mg po twice daily followed, on progression or toxicity, by sunitinib 50 mg po daily 4 wks on, 2 wks off or vice versa
Outcomes	PFS: primary outcome (time from randomisation to confirmed progression or death during second‐line therapy); secondary outcome (time from randomisation to confirmed progression or death during first‐line therapy) OS: secondary endpoint AE: reported in toxicity table QoL: not analysed RR: secondary outcome Other: disease control rate, total time to progression, time to first‐line treatment failure, cardiotoxicity
Funding Sources	German Cancer Society (DKG), Austrian Social Security Institutions, grants from industry study sponsor
Declarations of interest	Reported
Notes	Planned as a non‐inferiority study, amended to a superiority design; power reduced from 90% to 85% due to slower rate of events than expected
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Central randomisation via fax"
Allocation concealment (selection bias)	Low risk	"the person who generated the randomisation list was not involved in the study project management, monitoring, or data management."
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	Open label study design, participants and personnel not blinded to treatment; no effect on OS expected
Blinding of participants and personnel (performance bias) Subjective outcomes	High risk	Open label study design, participants and personnel not blinded to treatment; both arms treated with same drugs in different sequence
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Assessed by investigator; no effect on OS expected
Blinding of outcome assessment (detection bias) Subjective outcomes	High risk	PFS assessed by investigator
Incomplete outcome data (attrition bias) PFS, OS	Low risk	All patients reported, 5/7 did not receive treatment in first line
Incomplete outcome data (attrition bias) Response rate	Low risk	All patients reported, 5/7 did not receive treatment in first line
Incomplete outcome data (attrition bias) Serious and minor adverse events	Low risk	All treated patients in first and second line reported
Selective reporting (reporting bias)	Low risk	All planned outcomes reported
Other bias	Unclear risk	Study design changed from non‐inferiority design to superiority design after randomisation of 138 participants