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Investigating the Efficacy of EGFR-TKIs and Anti-VEGFR Combination in Advanced Non-Small Cell Lung Cancer: A
Prashant Sakharkar1, Sonali Kurup2, Subrata Deb1
1College of Pharmacy, Larkin University, Miami, FL 33169, USA.
Introduction:
The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with anti-vascular endothelial growth factor receptor (VEGFR) agents have shown improved survival outcomes in recent studies. However, its efficacy related to survival outcomes as a first- or second-line agent and based on generations remains to be explored. This study estimated the survival outcomes of EGFR-TKIs plus anti-VEGFR in combination in defined populations of advanced non-small cell lung cancer (NSCLC) patients overall, as a first- or second line of treatment, with different generations of EGFR-TKIs and EGFR-TKIs plus bevacizumab combination as a subgroup.
Methods:
A literature search was conducted using PubMed, SCOPUS, Cochrane Library, and ClinicalTrials.gov databases through June 2023 to identify primary research reporting the survival outcomes of EGFR-TKIs in combination with anti-VEGFR agents in patients with advanced NSCLC. Studies that were single-arm, published in non-English languages, and had missing data on survival outcomes were excluded. A meta-analysis was conducted to generate pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Methodological quality and risk of bias in studies were assessed using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool.
Results:
A total of 20 randomized controlled trials were included in the qualitative synthesis, and 11 (2182 participants) were included in the meta-analysis. Patients' median age ranged from 58 to 68 years; 36% to 70% of patients were female; most of them had IIIa/b to IV stage cancer. In meta-analyses, the EGFR-TKIs plus anti-VEGFR combination resulted in improved PFS (HR, 0.73; 95% CI: 0.61, 0.86; p < 0.00001) in patients with advanced NSCLC but had no impact on OS (HR, 0.93; 95% CI: 0.79, 1.10; p = 0.41). The first line of treatment and first-generation EGFR-TKIs with the combination also improved the PFS (HR, 0.64; 95% CI: 0.57, 0.71; p < 0.00001; HR, 0.63; 95% CI: 0.56, 0.71; p < 0.00001) respectively, however, had no impact on OS.
Conclusions:
Our meta-analysis indicated EGFR-TKIs with anti-VEGFR in combination not only improved overall PFS but also showed similar results to a first line and first-generation agent compared to EGFR-TKI alone.
Insights
Combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with anti-vascular endothelial growth factor receptor (VEGFR) agents improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC). This combination showed benefits particularly in first-line treatment and with first-generation EGFR-TKIs.
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with anti-vascular endothelial growth factor receptor (VEGFR) agents show promise in advanced non-small cell lung cancer (NSCLC).
- The efficacy of these combinations as first- or second-line treatments and across different EGFR-TKI generations requires further investigation.
Purpose of the Study:
- To estimate the survival outcomes of combining EGFR-TKIs with anti-VEGFR agents in advanced NSCLC patients.
- To analyze efficacy based on treatment line (first- or second-line), EGFR-TKI generation, and specific combinations like EGFR-TKIs plus bevacizumab.
Main Methods:
- A comprehensive literature search was performed across major databases (PubMed, SCOPUS, Cochrane Library, ClinicalTrials.gov) up to June 2023.
- Included were randomized controlled trials reporting survival outcomes; single-arm, non-English, and data-deficient studies were excluded.
- Meta-analysis was used to calculate pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), with risk of bias assessment.
Main Results:
- Eleven randomized controlled trials with 2182 participants were included in the meta-analysis.
- The combination of EGFR-TKIs plus anti-VEGFR significantly improved PFS (HR: 0.73) but did not impact OS (HR: 0.93) in advanced NSCLC.
- First-line treatment and first-generation EGFR-TKIs in combination demonstrated improved PFS (HR: 0.64 and 0.63, respectively) without affecting OS.
Conclusions:
- The combination of EGFR-TKIs with anti-VEGFR agents enhances overall progression-free survival in advanced NSCLC.
- This combination demonstrated comparable efficacy to EGFR-TKI monotherapy, particularly when used as a first-line treatment or with first-generation EGFR-TKIs.
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