Lilenbaum 2005.

Methods	Randomized phase III trial, open‐label Inclusion criteria Cytologically or histologically confirmed NSCLC Measurable or evaluable disease Stage IIIB (malignant effusion) or stage IV disease ≥ 18 years of age (no upper age restriction) PS: 0 to 2 as assessed according to CALGB criteria Adequate hematological, hepatic, and renal function Prior radiotherapy allowed if it did not encompass index lesion(s) and was completed ≥ 2 weeks before protocol enrollment Exclusion criteria Known brain metastasis Previous or concomitant malignancy, except for curatively treated carcinoma in situ of the cervix or breast, non‐melanoma skin cancer, and non‐recurrent primary tumor treated surgically > 5 years before enrollment HIV positive
Participants	P arm: 277 participants (ITT population)/78 elderly participants CP arm: 284 participants (ITT population)/77 elderly participants
Interventions	P arm: paclitaxel 225 mg/m2 over 3‐hour i.v. infusion, every 3 weeks for maximum of 6 cycles CP arm: carboplatin AUC6 over 30‐minute i.v. infusion plus paclitaxel 225 mg/m2 over 3‐hour i.v. infusion, every 3 weeks for maximum of 6 cycles Secondary prophylaxis with filgrastim used for participants who developed febrile neutropenia or grade 4 neutropenia lasting > 5 days for all subsequent cycles
Outcomes	Primary outcome Overall survival (defined from date of randomization to death). Study designed to have 80% power to detect 30% improvement in median survival from 7.3 months in the paclitaxel arm to 9.5 months in the paclitaxel and paclitaxel/carboplatin arm Secondary outcome Progression‐free survival: defined from date of randomization to disease progression, relapse, or death
Notes	Study planned for adult population and elderly subgroup
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was centralized at the CALGB data management centre in Durham, NC. Patient randomisation was stratified by stage (IIIB v IV v recurrent), PS (0 to 1 v 2), and age (< 70 v ≥70 years of age)"
Allocation concealment (selection bias)	Unclear risk	Allocation concealment not reported
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	Unclear risk	"Twenty‐three patients (3.9%) either withdrew from the study before receiving protocol therapy or were later found to be ineligible"
Selective reporting (reporting bias)	High risk	PFS and toxicity data not reported for the elderly subgroup
Other bias	Unclear risk	Study designed for the general population; elderly subgroup analysis planned