Efficacy and Treatment-related Adverse Events of Multi-targeted Tyrosine Kinase Inhibitors in Advanced Non-small-cell Lung Cancer: a Meta-analysis of Randomized Controlled Trials

Background: Multitargeted tyrosine kinase inhibitors (TKIs) are used to treat advanced non-small cell lung cancer (NSCLC). Their efficacy and safety have been studied in randomized controlled trials.

Aim: This meta-analysis aimed to summarize the most up-to-date evidence regarding the efficacy and adverse events of TKIs in NSCLC treatment.

Method: Randomized controlled trials were searched from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The intervention arm was the TKI-containing group, and the control arm was the TKI-free group. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival, and adverse events were extracted and synthesized. The last search was performed in April 2022. Two researchers independently screened articles, extracted data, and evaluated the quality of the included studies. The Cochrane risk-of-bias tool was used to assess the quality of each study. Random or fixed-effect models were used in statistical methods. I statistics were used to assess heterogeneity.

Results: Thirty-one studies (12,517 patients) were included. Compared to the control group, the TKI group had significantly higher ORR (relative risk RR 1.52, 95% confidence interval, CI [1.29, 1.80], P < 0.05), DCR (RR 1.34, 95%CI [1.19, 1.51], P < 0.05), and prolonged PFS (hazard ratio HR 0.67, 95%CI [0.59, 0.77], P < 0.05). The TKI group showed a higher rate of adverse events (RR 1.70, 95%CI [1.34, 2.16], P < 0.05) and grade 3-5 adverse events (RR 1.59, 95% CI [1.35, 1.88], P < 0.05).

Conclusion: TKIs could increase ORR and DCR and prolong PFS for advanced NSCLC. Adverse events should be closely monitored.