Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis

Abstract

Background:: We compared the response rates, survival rates, and safety profile of epidermal growth factor receptor (EGFR) inhibitors with non-targeted chemotherapy and older EGFR inhibitors when used to treat advanced nonsmall cell lung cancer (NSCLC) patients with activating EGFR mutations. Methods:: We searched PubMed, Cochrane Central Register of Controlled Trials, and clinicaltrial.gov for randomized controlled trials published until 11-Feb-2020. Treatment outcomes were compared between EGFR inhibitor and pooled comparator; a subgroup analysis compared outcomes between EGFR inhibitor and non-targeted chemotherapy, and between newer and older EGFR inhibitors. Results:: Twenty-one studies with 4,250 unique patients were included. Significantly higher objective response rate (ORR) (odds ratio (OR) 2.28; 95% CI 2.00-2.61), higher disease control rate (DCR) (OR 2.3; 95% CI 1.88-3.06), and longer progression-free survival (PFS) (Hazard ratio (HR) 0.56; 95% CI 0.52-0.60) were observed in the EGFR inhibitor group compared to the pooled comparator group. Subgroup analysis revealed that the ORR, DCR, and PFS were significantly higher with EGFR inhibitors than non-targeted chemotherapy, and only PFS (and not ORR and DCR) was significantly longer with newer EGFR inhibitors than the older EGFR inhibitors. Overall survival (OS) was not significantly different between EGFR inhibitors and pooled comparator (HR 0.91; 95% CI 0.83-1.00) as well as in either of the subgroup analyses. Adverse events ≥ grade 3 and treatment discontinuation were significantly higher with non-targeted chemotherapy compared to the EGFR inhibitors. Conclusions:: The benefits of prolongations of ORR, DCR, and PFS might not imply significantly improved OS after therapy with EGFR inhibitors when compared with non-targeted chemotherapy or older EGFR inhibitors.