Abstract
BackgroundLung cancer is a heterogeneous disease with multiple signaling pathways influencing tumor cell survival and proliferation, and it is likely that blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Whether combined inhibition therapy has greater anti-tumor activity than single inhibition therapy is a matter of debate. Hence, a meta-analysis comparing therapy inhibiting both VEGFR and EGFR signaling pathways with that inhibiting EGFR signaling pathway alone was performed.Methodology and Principal FindingsWe searched PubMed, EMBASE database and the proceedings of major conferences for relevant clinical trials. Outcomes analyzed were objective tumor response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Besides, subgroup analyses were performed to investigate whether the combined inhibition therapy is best performed using combination of selective agents or a single agent with multiple targets.Six trials recruiting 3,302 patients were included in the analysis. Combined inhibition therapy was associated with a 3% improvement in OS as compared with single-targeted therapy, but this difference was not statistically significant (HR, 0.97; 95% CI, 0.89–1.05; P = 0.472). Patients receiving combined inhibition therapy had significant longer PFS than the group with single-targeted therapy (HR, 0.80; 95% CI, 0.67–0.95; P = 0.011). There was no difference in the ORR between the groups (OR, 1.44; 95% CI, 0.95–2.18; P = 0.085). Subgroup analysis revealed that combined inhibition therapy using combination regimens was associated with statistically significant improvement in both ORR and PFS. Toxicity was greater in combined inhibition therapy.ConclusionsThere is no evidence to support the use of combined inhibition therapy in unselected patients with advanced NSCLC. However, given the significant advantage in ORR and PFS, combined inhibition therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.
Highlights
Non-small-cell lung cancer (NSCLC) accounts for approximately 80–85% of all cases of lung cancer, and is the most common cause of cancer death in industrialized countries [1]
There is no evidence to support the use of combined inhibition therapy in unselected patients with advanced NSCLC
Given the significant advantage in objective tumor response rate (ORR) and progression-free survival (PFS), combined inhibition therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment
Summary
Non-small-cell lung cancer (NSCLC) accounts for approximately 80–85% of all cases of lung cancer, and is the most common cause of cancer death in industrialized countries [1]. Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors are two key molecular targeted therapies in NSCLC. The EGFR is a receptor tyrosine kinase (TK) of the ErbB/ HER family It is expressed at high levels on the surface of many epithelial tumours, including NSCLC and is activated by a variety of ligands principally transforming growth factor alpha and epidermal growth factor [6]. Receptor activation signals key downstream pathways that regulate cell proliferation, differentiation, and survival [7]. Given their prominent role in tumour growth, invasion, and metastasis, the VEGFR and EGFR signaling pathway present feasible targets for pharmacologic intervention in NSCLC, and several agents have demonstrated encouraging antitumor activity. A meta-analysis comparing therapy inhibiting both VEGFR and EGFR signaling pathways with that inhibiting EGFR signaling pathway alone was performed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
