PMID- 36661266
OWN - NLM
STAT- MEDLINE
DCOM- 20230224
LR  - 20230903
IS  - 1537-453X (Electronic)
IS  - 0277-3732 (Linking)
VI  - 46
IP  - 3
DP  - 2023 Mar 1
TI  - Efficacy and Toxicity of Combined Inhibition of EGFR and VEGF in Patients With 
      Advanced Non-small Cell Lung Cancer Harboring Activating EGFR Mutations: A 
      Systematic Review and Meta-analysis.
PG  - 87-93
LID - 10.1097/COC.0000000000000976 [doi]
AB  - 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. We conducted a systematic 
      review and meta-analysis to assess the efficacy and toxicity of the combined 
      treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for 
      patients with advanced non-small cell lung cancer harboring activating EGFR 
      mutations, in comparison to EGFR TKIs alone. The electronic databases were 
      searched for relevant randomized trials between 2000 and 2022. The primary 
      endpoints were overall survival (OS) and progression-free survival. Secondary 
      endpoints included objective response rate (ORR), disease control rate, and grade 
      >/=3 adverse events (AEs). The pooled hazard ratios (HR) and odds ratios were 
      meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. 
      A total of 1528 patients from 8 trials were evaluated for analyses. The 
      combination treatment decreased the risk of disease progression by 37% (HR=0.63; 
      95% CI, 0.56 to 0.72) but had no added benefit on OS compared with EGFR 
      inhibition alone (HR=0.90; 95% CI, 0.76 to 1.05). There was no significant 
      difference in objective response rate or disease control rate between treatments. 
      There was a significantly increased number of AEs reported in the dual treatment 
      arm (odds ratio=3.02; 95% CI, 1.71 to 5.31), with proteinuria and hypertension 
      being the most significantly increased AEs. This meta-analysis suggests combined 
      inhibition of EGFR and VEGF pathways significantly improves progression-free 
      survival, with no OS benefit, and increases AEs. Mature OS data are needed along 
      with results from more trials exploring this strategy with third-generation EGFR 
      TKIs to strengthen these results.
CI  - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Deluce, Jasna
AU  - Deluce J
AD  - Division of Medical Oncology, Department of Oncology.
FAU - Maj, David
AU  - Maj D
AD  - Division of Medical Oncology, Department of Oncology.
AD  - Division of Clinical Pharmacology, Department of Medicine, Schulich School of 
      Medicine and Dentistry, Western University, London, ON, Canada.
FAU - Verma, Saurav
AU  - Verma S
AUID- ORCID: 0000-0002-8841-9820
AD  - Division of Medical Oncology, Department of Oncology.
FAU - Breadner, Daniel
AU  - Breadner D
AD  - Division of Medical Oncology, Department of Oncology.
FAU - Boldt, Gabriel
AU  - Boldt G
AD  - Division of Medical Oncology, Department of Oncology.
FAU - Raphael, Jacques
AU  - Raphael J
AD  - Division of Medical Oncology, Department of Oncology.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20230120
PL  - United States
TA  - Am J Clin Oncol
JT  - American journal of clinical oncology
JID - 8207754
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - EC 2.7.10.1 (EGFR protein, human)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Non-Small-Cell Lung
MH  - Vascular Endothelial Growth Factor A
MH  - *Lung Neoplasms
MH  - *Antineoplastic Agents/therapeutic use
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - ErbB Receptors/genetics
MH  - Vascular Endothelial Growth Factors/genetics/therapeutic use
MH  - Mutation
COIS- D.B. has provided advisory board participation or received honoraria from Amgen 
      Canada, Bristol-Myers-Squibb, AstraZeneca, and Takeda. J.R. has provided advisory 
      board participation or received honoraria from Roche, Novartis, Merck, Lilly, and 
      AstraZeneca. The remaining authors declare no conflicts of interest.
EDAT- 2023/01/21 06:00
MHDA- 2023/02/25 06:00
CRDT- 2023/01/20 07:33
PHST- 2023/01/21 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2023/01/20 07:33 [entrez]
AID - 00000421-202303000-00001 [pii]
AID - 10.1097/COC.0000000000000976 [doi]
PST - ppublish
SO  - Am J Clin Oncol. 2023 Mar 1;46(3):87-93. doi: 10.1097/COC.0000000000000976. Epub 
      2023 Jan 20.