Efficacy and safety of anti-angiogenic drugs combined with erlotinib in the treatment of advanced non-small cell lung cancer: a meta-analysis of randomized clinical trials.

Abstract

To determine the efficacy and safety of anti-angiogenic drugs combined with erlotinib in the treatment of advanced non-small cell lung cancer (NSCLC), we performed a meta-analysis of 10 randomized controlled trials (RCTs). An electronic literature search of PubMed, Cochrane Library, Embase, and other databases was performed. Literature was retrieved on December 2, 2019. We collected and compared RCTs on antiangiogenic drugs combined with erlotinib (A + E) for NSCLC, and analyzed outcomes including overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and incidence of severe adverse events (grade ≥3 AEs). Compared with the control group, combined treatment did not increase the ORR (RR 1.03, 95% CI: 0.95-1.11, P=0.52) or prolong OS (HR 1.03, 95% CI: 0.91-1.17, P=0.24); however, a significant improvement was seen in PFS (HR 0.63, 95% CI: 0.57-0.70, P<0.001). The subgroup analysis showed that patients with epidermal growth factor receptor (EGFR) mutations and patients with adenocarcinoma could benefit from combination therapy, as could those from Asian populations. Although combination therapy was found to carry an increased incidence of grade 3 or higher adverse events including diarrhea and proteinuria, these remained within controllable levels. Anti-angiogenic drugs used in combination with erlotinib can significantly prolong PFS in patients with advanced NSCLC.