Gridelli 2003.

Methods	Randomized phase III open‐label trial Inclusion criteria ≥ 70 years of age Cytologically or histologically confirmed NSCLC Stage IIIB (with pleural effusion or metastatic supraclavicular lymph nodes) or IV disease ECOG 0 to 2 Adequate organ function Exclusion criteria Overt brain metastasis Prior chemotherapy
Participants	V arm: 233/median age at baseline: 74 (range 63 to 85) years; 19% ECOG 2 G arm: 233/median age at baseline: 74 (range 70 to 86) years; 18% ECOG 2 GV arm: 232/median age at baseline: 74 (range 69 to 84) years; 20% ECOG 2 > 70% of entire population had ADL score of 6; 50% had IADL score > 75%
Interventions	V arm: vinorelbine 30 mg/m2 i.v. infusion on days 1 and 8, every 3 weeks for maximum of 6 cycles G arm: gemcitabine 1200 mg/m2 i.v. infusion on days 1 and 8, every 3 weeks for maximum of 6 cycles GV arm: gemcitabine 1000 mg/m2 i.v. infusion on days 1 and 8 plus vinorelbine 25 mg/m2 i.v. infusion on days 1 and 8, every 3 weeks for maximum of 6 cycles
Outcomes	Primary outcome Overall survival (defined date from randomization to date of death or to date of study closure; for those lost to follow‐up at a given time, survival defined as time between date of randomization and last date on which participants were known to be alive Secondary outcomes Progression‐free survival (defined as date from randomization to date of disease progression or death from disease progression or unknown causes; for participants lost to follow‐up before disease progression, progression‐free survival defined as time between the date of randomization and date on whichparticipants were known to be free of disease progression) Response rate Toxicity Quality of life (using questionnaires QLQ‐C30 and QLQ‐LC13)
Notes	Statistical analysis planned to test whether GV was superior to each single agent separately (estimated 370 events to detect improvement from 27 weeks to 36 weeks on overall survival corresponding to HR 0.75, with 1‐tailed alpha error of 5%, power 0.87) Two geriatric scales (Active Daily Life (ADL) and Intrumental Active Daily Life (IADL)) completed by investigators at baseline and after third and sixth cycles Quality of life assessed by European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ‐C30) and Lung Cancer‐Specific Module (QLC‐LC13). Response and toxicity assessed by WHO criteria
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomisation was performed centrally at the Clinical Trials Office National Cancer Institute (Naples, Italy), using a computer‐generated procedure of minimization. Patients were stratified according to institution, ECOG, performance status (0, 1 or 2) and disease stage (IIIB versus IV)"
Allocation concealment (selection bias)	Unclear risk	Allocation concealment not mentioned
Blinding of outcome assessment (detection bias) OS and 1y OS rate outcome	Unclear risk	Open‐label study considered to have unclear impact on mortality outcomes
Blinding of outcome assessment (detection bias) Other outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias) All outcomes	Low risk	No evidence of attrition bias
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting
Other bias	Low risk	No evidence of other bias