Chemotherapy plus EGFR -TKIs versus EGFR -TKIs Alone in Non–small Cell Lung Cancer with EGFR -Activating Mutations: A Meta-analysis

Abstract

Targeted therapy based on the presence of activating epidermal growth factor receptor (EGFR) mutations is becoming standard practice in patients with advanced non-small cell lung cancer (NSCLC). However, whether the combination of EGFR Tyrosine Kinase Inhibitors (TKIs) and chemotherapy was better than EGFR-TKIs alone in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations remained controversial. This meta-analysis was conducted to assess the efficacy and safety of EGFR-TKIs plus chemotherapy versus EGFR-TKIs alone in NSCLC patients with EGFR-activating mutations. Search of PubMed, Cochran library and ClinicalTrials.gov website was performed for randomized clinical trials that compared EGFR-TKIs plus chemotherapy with EGFR-TKIs alone in NSCLC patients with EGFR-activating mutations from inception to 1st September. The main points of this meta-analysis were overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and grade 3 or 4 adverse effects (AE). A total of 1131 articles were cover at the initial search stage. After exclusion of duplicate, irrelevant studies and randomized controlled trials (RCTs) without adequate data, 5 studies that enrolled 862 patients were finally included in this meta-analysis. Our results showed that the combination of EGFR-TKIs and chemotherapy obviously improved the PFS in NSCLC patients with EGFR-activating mutations (hazard ratio [HR]=0.72, 95%CI=0.58-0.91, P=0.006). But, there was no significant difference between the two arms in ORR (HR=1.06, 95%CI=0.94-1.19, P=0.35) and OS (HR=0.95, 95%CI=0.52-1.71, P=0.85). In subgroup analysis, we found that combination therapy could improve PFS in Asian population (HR=0.69, 95%CI=0.54-0.89, P=0.004), however, it seemed that Caucasian population might not get benefit from this kind combined therapy (HR=0.89, 95%CI=0.51-1.56, P=0.69). Besides, the combined therapy also did not significantly improve the OS, no matter in Asian population (HR=1.00, 95%CI=0.65-1.54, P=0.99) or in Caucasian population (HR=1.00, 95%CI=0.42-2.37, P=1.00). In addition to, the incidences of grade 3 or 4 AE such as Diarrhea, Rash, Neutropenia and increasing of ALT or AST were low and similar between the two arms. The current available evidence indicated that the combination of EGFR-TKIs and chemotherapy is a potent choice without more toxicity for advanced NSCLC patients (especially for Asian patients) with EGFR-activating mutations. Further well-designed prospective randomized clinical trials are warranted to validate our results.