Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and meta-analysis

BACKGROUND Lung cancer is a major cause of death among patients, and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers in many countries. AIM To evaluate the clinical benefit (CB) of COX-2 inhibitors in patients with advanced NSCLC using systematic review. METHODS We searched the six electronic databases up until December 9, 2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC. Overall survival (OS), progression free survival (PFS), 1-year survival rate (SR), overall response rate (ORR), CB, complete response (CR), partial response (PR), stable disease (SD), and toxicities were measured with more than one outcome as their endpoints. Fixed and random effects models were used to calculate risk estimates in a meta-analysis. Potential publication bias was calculated using Egger’s linear regression test. Data analysis was performed using R software. RESULTS The COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS, progression free survival, 1-year SR, CB, CR, and SD. However, there was a difference in overall response rate for patients with advanced NSCLC. In a subgroup analysis, significantly increased ORR results were found for celecoxib, rofecoxib, first-line treatment, and PR. For adverse events, the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia, thrombocytopenia, and cardiovascular events. CONCLUSION COX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.