Kangai Injection Combined with Platinum-based Chemotherapy for the Treatment of Stage III/IV Non-Small Cell Lung Cancer: A Meta-analysis and Systematic Review of 35 Randomized Controlled Trials

Abstract

Objective: In an effort to inform evidence-based guidelines for clinical practice, we performed a meta-analysis to systematically evaluate the safety and efficacy of Kangai injection (KAI) plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer (NSCLC). Methods: Randomized controlled trials (RCTs) comparing KAI plus platinum-based chemotherapy (experimental group) to chemotherapy alone (control group) were electronically retrieved from the Cochrane Library, PubMed, EMbase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Biological Medicine (CBM) Database, Wanfang Database, and the VIP Database for Chinese Technical Periodicals. RCTs published from the date of inception to July 5, 2018, were included. All trials were assessed for methodological quality in accordance with the Cochrane Reviewer's Handbook for Systematic Reviews of Intervention. Meta-analysis was performed using RevMan5.3 Software and Comprehensive Meta-Analysis (CMA) 2.0. Results: The final analysis included 35 RCTs involving 2,618 patients. Our meta-analysis revealed that KAI combined with platinum-based chemotherapy was associated with significantly greater objective response rate (ORR) (RR=1.36, 95% CI: 1.25-1.49, P<0.00001) and disease control rate (DCR) (RR=1.14, 95% CI: 1.09-1.18, P<0.00001), improvements in quality of life (QOL) (RR=1.75, 95% CI: 1.59-1.93, P<0.00001), and decreases in the incidence of gastrointestinal reactions (RR=0.64, 95% CI: 0.54-0.77, P<0.00001), leukocytopenia (RR=0.54, 95% CI: 0.46-0.63, P<0.00001) and thrombocytopenia (RR=0.52, 95% CI: 0.36-0.76, P=0.0007) when compared with chemotherapy alone. In addition, combined treatment was associated with greater regulation of tumor immune function, as indicated by increases in the proportion of NK, CD₃ ⁺ , and CD₄ ⁺ cells (MD=2.27, 95% CI: 1.18-3.36, P<0.0001; MD=12.86, 95% CI: 11.64-14.08, P<0.00001; and MD=5.48, 95% CI: 2.68-8.28, P=0.0001) and decreases in the percentage of CD₈ ⁺ cells (MD= -2.37, 95% CI from -4.51 to -0.23, P=0.03). Conclusions: From the available evidence, our results indicate that KAI plus platinum-based chemotherapy could be more effective in improving clinical efficacy, decreasing the incidence of adverse reactions and regulating the tumor immune function than chemotherapy alone in the treatment of stage III/IV NSCLC. Nevertheless, considering the limitations of the included studies, rigorous designed, high-quality, multicenter clinical trials are still need to further confirm the results.

Keywords: Kangai injection; Meta-analysis; non-small cell lung cancer; platinum-based chemotherapy; systematic review.

Figure 1

Flow diagram of screening process for eligible articles.

Figure 2

Summary of the risk of bias for each included study. “+” (green): low risk of bias; “?” (yellow): unclear risk of bias; “-” (red): high risk of bias.

Figure 3

Risk of bias graph. Each risk of bias is presented as the percentage across all included studies.

Figure 4

Forest plot showing objective response rates (ORR).

Figure 5

Forest plot showing disease control rates (DCR).

Figure 6

Forest plot showing quality of life (QOL) results for the included studies.

Figure 7

Forest plot showing the incidence of gastrointestinal reactions for the included studies.

Figure 8

Forest plot showing rates of myelosuppression for the included studies: a. leukocytopenia; b. hemoglobin deficiency; c. thrombocytopenia.

Figure 9

Forest plot shows immune index. a. NK; b. CD3⁺; c. CD4⁺; d. CD8⁺; e. CD4⁺/CD8⁺.

Figure 10

Funnel plot of ORR.

Figure 11

Trial sequential analysis on ORR.

Figure 12

Meta-regression analysis on ORR.

Figure 13

Meta-regression analysis on QOL.