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Meta-Analysis
. 2017 Jan 3;8(1):1141-1155.
doi: 10.18632/oncotarget.13588.

Efficacy and safety of angiogenesis inhibitors in small-cell lung cancer

Heng Lin  1   2 , Lina Li  1 , Shuimei Luo  1 , Sijing Zhou  1 , Ruifen Shen  1 , Haitao Yang  1 , Huijuan Chen  1 , Xianhe Xie  1
Affiliations
Meta-Analysis

Efficacy and safety of angiogenesis inhibitors in small-cell lung cancer

Heng Lin et al. Oncotarget. .

Abstract

Objective: The purpose of this study was to investigate the efficacy and safety of angiogenesis inhibitors for small-cell lung cancer (SCLC).

Methods: Totally, 16 controlled trials (1898 cases) involving angiogenesis inhibitors plus chemotherapy (ACT group) versus chemotherapy alone group (CT group) were identified from PubMed, EMBASE, Cochrane Library and Wanfang Data before March 2016.

Results: Compared with CT group, ACT group obtained a significant benefit on objective response rate (ORR) (RR = 1.34; 95% CI = 1.19-1.51; P < 0.00001) and a trend of prolonging progression-free survival (PFS) (HR = 0.86; 95% CI = 0.73-1.01; P = 0.07) without improving overall survival (OS) (HR = 1.05; 95% CI = 0.94-1.17; P = 0.36). Remarkably, subgroup analysis showed that the antibodies targeting VEGF significantly prolonged PFS (HR = 0.76; 95% CI = 0.64-0.90; P = 0.001). With regard to toxicity, there was no significant difference in severe adverse events (AEs, Grade≥3) between two groups except that gastrointestinal symptom, hypertension, metabolic disorders, neurology and pain were higher in ACT group.

Conclusion: Compared with chemotherapy alone, antibodies targeting VEGF plus chemotherapy significantly improved ORR and prolonged PFS with an acceptable toxicity profile for patients with SCLC. Therefore, angiogenesis inhibitors, especially antibodies targeting VEGF, combining with chemotherapy may be a potential promising strategy in managing SCLC.

Keywords: angiogenesis inhibitors; chemotherapy; meta-analysis; small-cell lung cancer; targeted therapy.

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Conflict of interest statement

CONFLICTS OF INTEREST

There is no conflict of interest.

Figures

Figure 1
Figure 1. A flow chart on selection included trials in the Meta-analysis
Figure 2
Figure 2. Bias risk and quality assessment of included studies
Figure 3
Figure 3
A. Objective response rate (ORR) of the studies; B. Subgroup analysis of ORR for angiogenesis inhibitors only targeting VEGF/VEGFR plus chemotherapy (CT) versus CT.
Figure 4
Figure 4. Funnel plot of ORR for included studies
Figure 5
Figure 5
A. Overall survival (OS) of the studies; B. Subgroup analysis of the effect of angiogenesis inhibitors on OS in first-line settings; C. Subgroup analysis of OS for antibodies targeting VEGF plus CT versus CT; D. Subgroup analysis of OS for small molecule angiogenesis inhibitors plus CT versus CT.
Figure 6
Figure 6
A. Progression-free survival (PFS) of the studies; B. Subgroup analysis of the effect of angiogenesis inhibitors on PFS in first-line settings.
Figure 7
Figure 7
A. Subgroup analysis of PFS for antibodies targeting VEGF plus CT versus CT; B. Subgroup analysis of PFS for small molecule angiogenesis inhibitors plus CT versus CT; C. Subgroup analysis of PFS for angiogenesis inhibitors only targeting VEGF/VEGFR plus CT versus CT.
Figure 8
Figure 8. Severe hematologic toxicities of the studies
Figure 9
Figure 9. Severe nonhematologic toxicities of the studies (Part 1)
Figure 10
Figure 10. Severe nonhematologic toxicities of the studies (Part 2)
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