We retrieved and examined 336 descriptive reviews, 104 clinical trials, and 8 systematic reviews with metaanalysis in the preliminary evaluation. Fifteen of these 448 articles (all of them reporting data of randomized phase III clinical trials) were considered potentially eligible because they reported mature data comparing different therapeutic options in second-line treatment of NSCLC, and 14 were included into the analysis. Two of the 15 potentially eligible studies3,19 reported data from the same trial (the TAX317 trial) and were analyzed as a single report. Three trials comparing antineoplastic treatments with BSC were included in the primary analysis,3,16,17 and 11 trials7–13,20–24 comparing docetaxel administration every 3 weeks with other docetaxel schedules or ifosfamide/vinorelbine, pemetrexed, oral topotecan, paclitaxel poliglumex, vinflunine, gefitinib, or docetaxel-gemcitabine combination were included in the secondary analysis. One trial published in two different journals3,19 and included in the primary analysis as a single report (TAX317 trial) compared docetaxel administration every 3 weeks with BSC, one trial16 compared gefitinib with placebo (the Iressa Survival Evalaution in Lung Cancer [ISEL] trial), and one trial17 compared erlotinib with placebo (BR-21 trial). As concerns the secondary analysis, docetaxel every 3 weeks was compared with ifosfamide or vinorelbine in one trial (TAX320 trial),7 with weekly docetaxel in three trials,8–10 with pemetrexed in one trial,12 with oral topotecan in one trial,13 with paclitaxel poliglumex in one trial,20 with vinflunine in one trial,21 with gefitinib in two trials,22,23 and with the docetaxel-gemcitabine combination in one trial.24 Six trials included in the secondary analysis were published as full-text articles in peer-reviewed journals,7–10,12,13 and five trials were published as abstracts in congress proceedings.20–24 The main characteristics of the trials and main inclusion criteria are detailed in Table 2. The Nicolucci score of the nine eligible full-text published trials ranged from 54 to 89%, with a median value of 70% (Table 2). The recruitment in the trials included in the primary analysis began in 1994 (TAX317 trial)3 and concluded in 2004 (ISEL trial)16; the recruitment in the trials included in the secondary analysis began in 1995 (TAX320 trial)7 and concluded in 2003 (the trials of Schuette et al,9 Camps et al,10 and Ramlau et al13). All the trials published as full-text articles reported data about age, sex, and ECOG performance status of the patients.3,7–13,16,17 The RR to first-line chemotherapy was reported in the TAX317,3 ISEL,16 BR21,17 Gridelli et al,8 and Hanna et al12 trials; in the TAX320 trial,7 it was reported as a complete and partial response plus stable disease. The histologic type was reported in the ISEL,16 BR21,17 Schuette et al,9 Chen et al,11 Hanna et al,12 and Ramlau et al13 trials.9,11–13,16,17 The “never-smoker” status was reported in the ISEL16 and BR21 trials.17 The main prognostic factors reported in the trials published as full-text articles are detailed in Table 3. No univocal data about the main prognostic factor could be extracted from congress proceedings. The outcomes of 2,627 patients were analyzed in the primary analysis, and those of 5,952 patients in the secondary analysis (Fig 1).