Abstract 1358P
Background
Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways have demonstrated promising results for treatment of advanced non-small cell lung cancer (NSCLC). We conducted a systematic review and meta-analysis to assess the efficacy and toxicity of combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF monoclonal antibodies for patients harboring activating EGFR mutations.
Methods
The electronic databases PubMed, Cochrane and EMBASE were searched for relevant randomized trials between 2000 and 2019. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and grade 3 or higher adverse events (AEs). Pooled hazard ratios (HR) for OS and PFS and odds ratios (OR) for ORR, DCR and toxicity were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. Random-effect models were used to compute pooled estimates. Subgroup analyses compared PFS by gender, age, smoking status, type of EGFR mutation, intracranial disease and ECOG performance status.
Results
A total of 1,246 patients from 6 trials were evaluated for analyses. Compared to EGFR inhibition alone, combination treatment decreased the risk of disease progression (PFS) (HR=0.64; 95%CI 0.55-0.75), but not OS (HR=0.90; 95%CI 0.68-1.19). There were a significantly increased number of AEs reported in the dual treatment arm (OR=3.55; 95%CI 2.74-4.59), with proteinuria (OR=14.55; 95%CI 4.47-47.4) and hypertension (OR=7.02; 95%CI 4.73-10.43) being the most significantly increased AEs. Furthermore, no difference in ORR (OR=0.86; 95%CI 0.65-1.12) and DCR (OR=0.75; 95%CI 0.41-1.39) were found. The PFS benefit was consistent across all subgroups.
Conclusions
This study suggests combined inhibition of EGFR and VEGF pathways significantly improves PFS, with no OS benefit demonstrated, and increases AEs. Mature OS data are needed to strengthen these results along with results from newer trials exploring this strategy with 3rd generation EGFR-TKIs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.