The Impact of Histological Types on the Efficacy of Angiogenesis Inhibitors in the Treatment of Advanced NSCLC: A Meta-Analysis of Randomized Controlled Trials

Overall survival

For patients with lung adenocarcinoma, seven of the 13 trials with a total of 4,457 patients reported OS data. The pooled results demonstrated that the use of AIs significantly improve OS in comparison with non-AI-containing therapies (HR, 0.92, 95% CI: 0.85–0.99, P=0.017, Figure 2 and Table 2) using a fixed-effects model (I2=0%). A total of 1,796 squamous cell cancer (SCC) patients from nine trials reported OS data, and the pooled results found that AI-containing regimens did not improve OS in comparison with non-AI-containing regimens (HR, 1.02, 95% CI: 0.92–1.15, P=0.68, Figure 2 and Table 2) using a fixed-effects model (I2=24.3%). Additionally, a nonsignificantly improved OS was observed in NSCLC patients with other histologies who were treated with AI-containing therapies (HR, 0.90, 95% CI: 0.76–1.08, P=0.19, Figure 2 and Table 2). We then performed subgroup analysis according to treatment line. Our results showed that the use of AIs as second-line therapy in adenocarcinoma significantly improved OS (HR, 0.93, 95% CI: 0.86–1.00, P=0.05), while only one trial using AIs as first-line therapy in adenocarcinoma was included for analysis, and a tendency to improve OS was also observed (HR, 0.88, 95% CI: 0.75–1.03, P=0.11). For SCC patients, the use of AIs as second-line therapy seemed to improve OS (HR, 0.97, 95% CI: 0.86–1.10, P=0.66). However, the use of AIs as first-line therapy in these patients tended to decrease OS (HR, 1.25, 95% CI: 0.97–1.60, P=0.08).

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Progression-free survival

A total of 3,692 lung adenocarcinoma and 1,354 SCC patients were included for analysis. The pooled HR for PFS demonstrated that AI-containing therapies significantly improve PFS in lung adenocarcinoma (HR, 0.84, 95% CI: 0.78–0.91, P<0.001, Figure 3 and Table 2) and SCC (HR, 0.87, 95% CI: 0.77–0.98, P=0.027, Figure 2 and Table 2), compared with non-AIs containing therapy. There was moderate heterogeneity between trials (I2=43.9% and 46.2%), and the pooled HR for PFS was performed by using fixed-effects model. For patients with other histologies, the pooled results did not significantly improve PFS when compared to non-AI-containing regimens (HR, 0.90; 95% CI: 0.75–1.09, P=0.27, Figure 2 and Table 2).

(To view a larger version of Figure 3, click here.)