OBJECTIVES: Objective response rate (ORR) is an early indicator of successful treatment in patients with NSCLC. This research compared gefitinib with platinum-based doublet chemotherapies for first-line treatment of advanced NSCLC in patients harbouring activating epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations (M+).  METHODS: Systematic searching of CENTRAL, EMBASE and MEDLINE for randomised controlled trials (RCTs) comparing ≥ 2 doublet chemotherapies (carboplatin or cisplatin in combination with either docetaxel, gemcitabine, paclitaxel, pemetrexed, or vinorelbine) for the first-line treatment of advanced NSCLC was completed in May 2009. A meta-analysis was performed on ORR using data from published RCTs of gefitinib vs paclitaxel/carboplatin in EGFR-TK M+ patients. A Mixed Treatment Comparison (MTC) was carried out with doublet chemotherapies in unselected advanced NSCLC patients using paclitaxel/carboplatin as a baseline. Treatment effect was calculated as an odds ratio (OR) with 95% Credible Interval (95%CrI). A sensitivity analysis was conducted on the inclusion of the gefitinib trials within the MTC. For this analysis it was assumed that the efficacy of doublet chemotherapy is consistently affected by EGFR-TK mutation status. RESULTS: Three RCTs were identified for gefitinib, of which two were comparisons with paclitaxel/carboplatin. Meta-analysis of these two trials gave an estimated ORR favouring gefitinib: OR 4.04, 95% Confidence Interval: 2.73-5.98. Twenty-nine trials were appropriate for inclusion in the MTC, of which 25 reported ORR. The MTC found no significant difference in ORR among other doublet chemotherapies vs paclitaxel/carboplatin, with the exception of pemetrexed/cisplatin, in patients with predominantly non-squamous tumour cell histology, which was associated with a significantly higher ORR (OR 1.64, 95%CrI: 1.15-2.27). In the sensitivity analysis, ORR was significantly higher with gefitinib vs all doublet chemotherapies (gefitinib vs pemetrexed/cisplatin OR 3.05, 95%CrI: 1.58-5.51). CONCLUSIONS: This adjusted indirect comparison suggests that gefitinib may have important ORR advantages over other first-line treatments in EGFR-TK M+ patients.