Smit 2003.

Methods	Randomized multi‐center, phase III trial Eligible patients Histologically or cytologically confirmed NSCLC Stage IIIB (supraclavicular nodal metastasis only or malignant pleural effusion) or IV Measurable disease No previous chemotherapy with exception of prior neoadjuvant or adjuvant chemotherapy that ended 1 year before entry > 18 to 76 years of age PS: 0 to 2 Previous radiotherapy allowed provided interval ≥ 4 weeks had elapsed and radiation field did not include all measurable lesions used as target lesion Brain or leptomeningeal metastasis allowed provided stable disease and asymptomatic after radiotherapy
Participants	CP arm: 159 participants (ITT population) ‐ median age (range): 57 (27 to 75) years/elderly participants not reported CG arm: 160 participants (ITT population) ‐ median age (range): 57 (28 to 75) years/elderly participants not reported GP arm: 161 participants (ITT population) ‐ median age (range): 56 (31 to 75) years/elderly participants not reported
Interventions	CP arm: cisplatin 80 mg/m2 i.v. infusion on day 1 plus paclitaxel 175 mg/m2 over 3‐hour i.v. infusion on day 1, every 3 weeks CG arm: cisplatin 80 mg/m2 i.v. infusion on day 1 plus gemcitabine 1250 mg/m2 over 30‐minute i.v. infusion on days 1 and 8, every 3 weeks GP arm: paclitaxel 175 mg/m2 over 3‐hour i.v. infusion on day 1 plus gemcitabine 1250 mg/m2 over 30‐minute i.v. infusion on days 1 and 8, every 3 weeks Prophylactic antiemetics during and after cisplatin administration, typically ondansetron and dexamethasone. Responding participants received maximum of 6 cycles
Outcomes	Primary outcome Overall survival (pair‐wise comparison between CG arm vs CP arm and GP arm vs CP arm) Secondary outcomes Progression‐free survival Response rate Duration of response Toxicity Quality of life (QoL) ‐ using EORTC QoL core questionnaire (QLC‐Q30) in conjunction with EORTC Lung Module (LC‐13) Cost of treatment
Notes	No information on inclusion of elderly patients nor on specific subgroup analysis, despite multiple attempts to contact study authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was performed centrally by the EORTC Data Center after stratification for PS (0 to 1 v 2), stage of disease (IIIB v IV), and institute, using the minimization technique"
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	No information on blinding
Blinding of outcome assessment (detection bias) Other outcomes	High risk	No information on blinding
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No evidence of attrition bias
Selective reporting (reporting bias)	Low risk	No evidence of reporting bias
Other bias	Unclear risk	Study designed for the general population; elderly subgroup analysis not planned