Rini 2019a.

Study characteristics
Methods	Study design: multicentre RCT Phase: 3 Accrual period: October 2016 to January 2018 Blinding: open label design Strata: IMDC risk group (favourable, intermediate, or poor risk) and geographic region IMC: an independent data and safety monitoring committee oversaw the trial Crossover: not planned
Participants	Histology: clear‐cell renal‐cell carcinoma Prior systemic therapy: treatment‐naïve Eligible PS: Karnowsky PS 70% or better Measurable disease: required Non metastatic %: < 99 M/F: 628/233 Age median (range): 62 (26 to 90) Prior nephrectomy: 715 Prognostic strata: system, good/intermediate/poor risk %: IMDC, 269/484/108
Interventions	Pembrolizumab 200 mg intravenously every 3 weeks plus Axitinib 5 mg orally twice daily versus Sunitinib 50 mg orally once daily for 4 weeks and then are off treatment for 2 weeks
Outcomes	PFS: co‐primary outcome assessed by blinded, independent central review OS: co‐primary outcome assessed by blinded, independent central review AE: reported in toxicity table, secondary outcome QoL: not assessed RR: secondary outcome assessed by blinded, independent central review Other: duration of response
Funding Sources	Industry sponsored
Declarations of interest	Reported online
Notes	Planned accrual completed, primary endpoint for OS not met because of short follow up
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Treatment randomization will occur centrally using an interactive voice response system / integrated web response system (IVRS/IWRS)" from protocol
Allocation concealment (selection bias)	Low risk	"Treatment randomization will occur centrally using an interactive voice response system / integrated web response system (IVRS/IWRS)" from protocol; central randomisation
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	"In this open‐label, phase 3 trial..." participants and personnel were not blinded to treatment, no effect on OS expected
Blinding of participants and personnel (performance bias) Subjective outcomes	High risk	"In this open‐label, phase 3 trial..." different drugs and administration form, participants and personnel were not blinded to treatment
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	OS assessed by blinded, independent central review
Blinding of outcome assessment (detection bias) Subjective outcomes	Low risk	Subjective primary and secondary efficacy endpoints assessed by blinded, independent central review
Incomplete outcome data (attrition bias) PFS, OS	Low risk	Intention to treat population analysed; < 1% in both groups did not receive treatment
Incomplete outcome data (attrition bias) Response rate	Low risk	Intention to treat population analysed; < 1% in both groups did not receive treatment
Incomplete outcome data (attrition bias) Serious and minor adverse events	Low risk	All treated participants reported in toxicity table
Selective reporting (reporting bias)	Low risk	All planned outcomes reported, no mature OS data available
Other bias	Low risk	Not detected