Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis

Abstract

Objectives: Our meta-analysis performed a systematic evaluation on the therapeutic efficacy and safety of tumour vaccines for the treatment of advanced non-small cell lung cancer (NSCLC).

Design: Systematic review and meta-analysis of randomised controlled trials (RCT).

Data sources: PubMed, the Cochrane Center Register of Controlled Trials, Science Direct and EMBASE were searched from January 1980 until January 2015.

Eligibility criteria for selecting studies: RCT were included; the control arm had to receive either placebo or chemotherapy or no treatment.

Main outcome measures: The quality of the data from individual papers was assessed for overall survival (OS), clinical response rate and side effects.

Results: Overall, 11 RCT of advanced NSCLC with a total of 3986 patients were conducted for meta-analysis. The results showed that the vaccine arm significantly extended primary endpoint median overall survival compared with control group (p<0.00001) (HR 0.760; 95% CI 0.644 to 0.896; p=0.001). Three subgroup patients with tumour vaccine at 1-year, 2-year and 3-year survival rates also gained significant benefits compared with their corresponding control group (p=0.0004, 0.03 and 0.19, respectively). Besides, a significant improvement in median time to progression (TTP), median progression-free survival (PFS) and a trend of improvement in objective response rate were observed after tumour vaccine treatment (p=0.001, 0.005 and 0.05, respectively; median PFS HR 0.842; 95% CI 0.744 to 0.954; p=0.007). A few severe adverse effects occurred in the tumour vaccine group, but fewer side effects were observed in the vaccine group compared with the control group (p<0.00001).

Conclusions: Taken together, NSCLC tumour vaccines markedly prolong median OS (p<0.00001), median TTP (p=0.001) and median PFS (p=0.005), improve clinical response rate (p=0.05) and lessen adverse side effects (p<0.00001). Our meta-analysis suggests tumour vaccines improve the efficacy of the treatment, and also provide superiority in treatment of patients with advanced NSCLC among a variety of immunotherapy strategies.

Keywords: Immunotherapy; Non-small cell lung cancer; Tumor vaccine.

Figure 1

Flow diagram of the study selection process.

Figure 2

Forest plot comparing the 1-year, 2-year and 3-year overall survival (OS) between the tumour vaccine group and control group. Owing to the low heterogeneity detected, the random effects model was used in this OS meta-analysis.

Figure 3

Comparison of the objective response rate (ORR) between the tumour vaccine group and control group. The random effects model was used. Significant difference: p value <0.05.

Figure 4

Forest plot comparing the toxicity and treatment-related side effects between the tumour vaccine group and control group. The random effects meta-analysis model was used in this analysis.

Figure 5

Forest plot comparing the severe side effects (grades ≥3) between the tumour vaccine group and control group. Some serious adverse effects occurred equally in both groups. The random effects meta-analysis model was used in this analysis.