Intercalated Combination of Chemotherapy and EGFR-TKIs versus Chemotherapy Alone in the First-line Treatment of Advanced Non-small Cell Lung Cancer: A Meta-analysis

Abstract

Background and objective The combination therapy of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has attracted the attention of more and more investigators. The aim of this meta-analysis is to evaluate the clinical efficacy and safety of intercalated combination of chemotherapy and EGFR- TKIs versus chemotherapy alone in the first-line therapy of advanced non-small cell lung cancer (NSCLC). Methods We retrieved the Cochrane Library, PubMed, EMBASE, CBM, CNKI and Wanfang databases for randomized controlled trials which involved the intercalated combination of chemotherapy and EGFR-TKIs, and chemotherapy alone in the first-line treatment of advanced NSCLC. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events were analyzed. The quality evaluation and cross-checked data were independently performed by two investigators according to the Cochrane Systematic Reviews Handbook. The Stata 12.0 software was used to conduct the meta-analysis. Results This study included 933 NSCLC patients from 6 RCTs. The meta-analysis demonstrated that the intercalated combination of chemotherapy and EGFR-TKIs significantly prolonged the PFS (HR=0.72, 95%CI: 0.53-0.98, P=0.037) of advanced NSCLC patients compared with mono-chemotherapy. However, there was no statistical difference in OS (HR=0.85, 95%CI: 0.72-1.01, P=0.060), ORR (OR=1.59, 95%CI: 0.86-2.95, P=0.142) and DCR (OR=1.09, 95%CI: 0.95-1.25, P=0.226) between the two groups. Further, the subgroup analysis showed that the intercalated combination markedly improved the PFS in female, adenocarcinoma, never smoking, EGFR mutant patients. In the aspect of safety, the main side effects of the intercalated combination therapy were rash (OR=7.81, 95%CI: 3.74-16.34, P<0.001) and diarrhea (OR=2.73, 95%CI: 1.92-3.89, P<0.001). Conclusion The intercalated combination of chemotherapy and EGFR-TKIs significantly prolonged the PFS in the first-line therapy of advanced NSCLC patients compared with mono-chemotherapy, and the main adverse events were tolerable rash and diarrhea. Together, the intercalated combination shows promising results, and more large-scale and high-quality RCTs are still needed.

Keywords

• Lung neoplasms
• Chemotherapy
• Epidermal growth factor receptor-tyrosine kinase inhibitors
• Intercalated combination
• First-line treatment
• Meta-analysis