TY - JOUR
T1 - Combining anti-epidermal growth factor receptor (EGFR) and anti-angiogenic strategies in advanced NSCLC
T2 - We should have known better...
AU - Di Maio, Massimo
AU - Morabito, Alessandro
AU - Piccirillo, Maria Carmela
AU - Daniele, Gennaro
AU - Giordano, Pasqualina
AU - Costanzo, Raffaele
AU - Sandomenico, Claudia
AU - Montanino, Agnese
AU - Rocco, Gaetano
AU - Perrone, Francesco
PY - 2014
Y1 - 2014
N2 - Drugs directed against Epidermal Growth Factor Receptor (EGFR), namely tyrosine kinase inhibitors erlotinib and gefitinib, and anti-angiogenic agents, namely the anti-Vascular Endothelial Growth Factor (VEGF) antibody bevacizumab, have independently demonstrated clinical benefit in the treatment of patients with advanced non-small cell lung cancer (NSCLC), and are currently approved for use in clinical practice. Pre-clinical studies have shown promising results with the combination of anti-EGFR and anti-angiogenesis drugs in different tumor models, including NSCLC. Several clinical trials have been conducted to verify if the combination of the two therapeutic strategies could improve the outcome in the setting of advanced NSCLC. The largest body of evidence has been produced testing the combination of erlotinib plus bevacizumab, or erlotinib plus a multi-targeted receptor tyrosine kinase inhibitor, namely sunit-inib or sorafenib. Furthermore, several dual inhibitors, targeting both EGFR and VEGFR, have been tested in advanced NSCLC, with the greatest body of evidence produced with vandetanib. However, despite an intriguing pre-clinical background, the combination strategy has not yet produced clinically relevant results. Several phase III trials showed an improvement in progression-free survival, underlining some activity of targeting both pathways concurrently, but no trial has demonstrated an impact on overall survival to date. Unfortunately, the vast majority of trials conducted in this setting have been performed without any selection criteria based on molecular characteristics, compromising the chance of detecting a potentially relevant benefit in selected subgroup of patients. In recent years, the important interaction between the efficacy of EGFR inhibitors and the presence of EGFR activating mutations in tumor cells has been repeatedly demonstrated. On the other hand, we still have no clear idea about predictive factors of efficacy for bevacizumab and other anti-angiogenic drugs. This is probably the real challenge to optimize the use of these drugs and to fully evaluate the real clinical potential of a combination strategy.
AB - Drugs directed against Epidermal Growth Factor Receptor (EGFR), namely tyrosine kinase inhibitors erlotinib and gefitinib, and anti-angiogenic agents, namely the anti-Vascular Endothelial Growth Factor (VEGF) antibody bevacizumab, have independently demonstrated clinical benefit in the treatment of patients with advanced non-small cell lung cancer (NSCLC), and are currently approved for use in clinical practice. Pre-clinical studies have shown promising results with the combination of anti-EGFR and anti-angiogenesis drugs in different tumor models, including NSCLC. Several clinical trials have been conducted to verify if the combination of the two therapeutic strategies could improve the outcome in the setting of advanced NSCLC. The largest body of evidence has been produced testing the combination of erlotinib plus bevacizumab, or erlotinib plus a multi-targeted receptor tyrosine kinase inhibitor, namely sunit-inib or sorafenib. Furthermore, several dual inhibitors, targeting both EGFR and VEGFR, have been tested in advanced NSCLC, with the greatest body of evidence produced with vandetanib. However, despite an intriguing pre-clinical background, the combination strategy has not yet produced clinically relevant results. Several phase III trials showed an improvement in progression-free survival, underlining some activity of targeting both pathways concurrently, but no trial has demonstrated an impact on overall survival to date. Unfortunately, the vast majority of trials conducted in this setting have been performed without any selection criteria based on molecular characteristics, compromising the chance of detecting a potentially relevant benefit in selected subgroup of patients. In recent years, the important interaction between the efficacy of EGFR inhibitors and the presence of EGFR activating mutations in tumor cells has been repeatedly demonstrated. On the other hand, we still have no clear idea about predictive factors of efficacy for bevacizumab and other anti-angiogenic drugs. This is probably the real challenge to optimize the use of these drugs and to fully evaluate the real clinical potential of a combination strategy.
KW - Advanced NSCLC
KW - Anti-angiogenesis
KW - Bevacizumab
KW - EGFR inhibition
KW - Erlotinib
KW - Gefitinib
KW - Sorafenib
KW - Sunitinib
KW - Vandetanib
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UR - http://www.scopus.com/inward/citedby.url?scp=84903985897&partnerID=8YFLogxK
U2 - 10.2174/13816128113196660762
DO - 10.2174/13816128113196660762
M3 - Article
C2 - 24191956
AN - SCOPUS:84903985897
VL - 20
SP - 3901
EP - 3913
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
SN - 1381-6128
IS - 24
ER -