Abstract
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) might be new therapeutic strategies for advanced non-small cell lung cancer (NSCLC). Here a total of 12,520 patients from 23 randomized controlled trials (RCTs) were enrolled to evaluate the efficacy and safety of VEGFR-TKIs quantitatively in advanced NSCLC. Compared with non-VEGFR-TKIs, VEGFR-TKIs regimen significantly improved progression-free survival (PFS) [hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.805-0.874, P < 0.001], objective response rates (ORR) [relative risk (RR): 1.374, 95%CI: 1.193-1.583, P < 0.001] and disease control rates (DCR) (RR: 1.113, 95%CI: 1.027-1.206, P =0.009), but not overall survival (OS) (HR: 0.960, 95%CI: 0.921-1.002, P =0.060) for NSCLC patients. The RR of all-grade neutropenia, thrombocytopenia, hypertension, hemorrhage, fatigue, anorexia, stomatitis, diarrhea, rash, hand-foot skin reaction (HFSR) were increased in patients received VEGFR-TKIs. As for high-grade (≥3) adverse events (AEs), VEGFR-TKIs were associated with higher RR of neutropenia, thrombocytopenia, hypertension, fatigue, stomatitis, diarrhea, rash and HFSR. This study demonstrates VEGFR-TKIs improve PFS, ORR and DCR, but not OS in advanced NSCLC patients. VEGFR-TKIs induce more frequent and serious AEs compared with control therapies.
Highlights
Standard therapy for advanced non-small cell lung cancer (NSCLC) is platinumbased palliative chemotherapy
These randomized controlled trials (RCTs) enrolled a total of 12,520 patients (VEGFR-TKIs arm: 6487, control arm:6033)
vascular endothelial growth factor recepter (VEGFR)-TKIs were compared with placebo in 6 trials and 17 trials were chemotherapy plus VEGFR-TKIs versus chemotherapy alone
Summary
Standard therapy for advanced NSCLC is platinumbased palliative chemotherapy. The “one size fits all” treatment model must be changed. Progress of NSCLC biology promoted the development of targeted agents. Those targeted agents inhibit vital signaling pathways, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor recepter (VEGFR) [3]. Targeted therapies have emerged as novel therapeutic options and changed the treatment paradigm of NSCLC. VEGFR, a critical pathway in tumor progression, represents an important target in NSCLC [4]. There are two major categories of agents targeting VEGFR pathway: VEGF antibodies and VEGFR tyrosine kinase inhibitors (VEGFR-TKIs)
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