Quoix 2011b.

Methods	Randomized phase III trial, multi‐center, open‐label Inclusion criteria 70 to 89 years of age, with cytologically or histologically confirmed non‐small cell lung cancer Stage IV or III unsuitable for radical therapy PS: 0 to 2, with adequate hematological, hepatic, and renal function and life expectancy ≥ 12 weeks Previous radiation therapy at symptomatic sites if completed ≥ 3 weeks before inclusion Asymptomatic brain metastases Exclusion criteria Active malignancy within past 5 years Previous chemotherapy Peripheral neuropathy ≥ grade 2 Co‐morbidities that impaired administration of chemotherapy or respiratory impairment that required long‐term oxygen delivery
Participants	Monotherpy arm: 226 Doublet chemotherapy arm: 255 Baseline characteristics for intention‐to‐treat population: median age: 77.1 (range 70.0 to 88.8) years; 27.3% (123) ECOG of 2, 20.1% (88) with ADL score < 6, 15.2% (67) with MMSE < 23, 24.4% (110) with Charlson index > 2
Interventions	Monotherapy arm: vinorelbine 25 mg/m2 i.v. infusion on days 1 and 8 or gemcitabine 1150 mg/m2 on days 1 and 8, every 3 weeks for maximum of 5 cycles Doublet chemotherapy arm: carboplatin AUC6 i.v. infusion on day 1 plus paclitaxel 90 mg/m2 i.v. infusion on days 1, 8, and 15, every 4 weeks for maximum of 4 cycles Primary prophylaxis with growth factor support not recommended, but secondary prophylaxis allowed for participants who developed grade 3 or 4 neutropenia in previous cycles
Outcomes	Primary outcome Overall survival (defined from date of randomization to death) Secondary outcomes Progression‐free survival (defined from date of randomization to disease progression or death, whichever occurred first) Response at week 6 Toxicity (grades 3 and 4)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomisation was done centrally by computer. We used the minimisation method and stratified patients by study centre, WHO performance status score (0–1 vs 2), stage (III vs IV), and age (≤̀80 vs >80 years)"
Allocation concealment (selection bias)	Unclear risk	No information on allocation concealment
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	Response reviewed through investigator panels. No information on toxicity and quality of life assessments
Incomplete outcome data (attrition bias) All outcomes	Low risk	Before the start of treatment, 1 participant excluded from the monotherapy and 2 from doublet chemotherapy group
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting bias
Other bias	Low risk	No evidence of other bias