Efficacy of combining targeted therapy with pemetrexed or docetaxel as second-line treatment in patients with advanced non-small-cell lung cancer: a meta-analysis of 14 randomized controlled trials

Abstract

Objectives: To compare the effects of adding targeted agents to standard second-line chemotherapy with a single agent (pemetrexed or docetaxel) in patients with advanced NSCLC, a meta-analysis of all relevant randomized controlled trials was performed and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were assessed.

Patients and methods: The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and December 2013. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.

Results: Fourteen trials with a total of 6922 patients were included in this meta-analysis. Compared with chemotherapy, combination therapy did not improve OS (HR = 0.95; 95% CI, 0.90-1.01; P = 0.081) but improved PFS (HR = 0.83; 95% CI, 0.78-0.87; P = 0.000). Survival outcomes did not differ significantly among trials. Combination therapy significantly increased ORR (RR = 1.83; 95% CI, 1.59-2.127; P = 0.000) and DCR (RR = 1.18; 95% CI, 1.13-1.23, P = 0.000). Sub-analysis indicated that adding targeted therapy to chemotherapy significantly prolonged OS in patients with non-squamous NSCLC (HR = 0.87; 95% CI, 0.87-0.97; P = 0.009). Patients treated with combination therapy had an increased incidence of grade 3 or greater diarrhea (RR = 1.96; 95% CI, 1.37-2.81; P = 0.000), neutropenia (RR = 1.27, 95% CI, 1.14-1.61; P = 0.000) and thrombocytopenia (RR = 4.21, 95% CI, 1.87-9.51; P = 0.001). This meta-analysis has the limitations of heterogeneity among the included trials and not using individual patient data.

Conclusions: In the second-line treatment of advanced NSCLC, the combination of targeted therapy and chemotherapy significantly increased response rates and progression-free survival, but did not improve overall survival and was more toxic.

Keywords: Advanced non-small-cell lung cancer; Chemotherapy; Efficacy; Meta-analysis; Targeted therapy; toxicity.