TY - JOUR
T1 - Motesanib and advanced NSCLC
T2 - Experiences and expectations
AU - Raghav, Kanwal Pratap Singh
AU - Blumenschein, George R.
N1 - Funding Information:
G Blumenschein has received research funding from Bayer, Genentech, GlaxoSmithKline, Merck and Pfizer. He has been a consultant for Amgen, Abbott and Bayer. K Raghav declares no conflicts of interest.
PY - 2011/6
Y1 - 2011/6
N2 - Introduction: Benefits from conventional chemotherapy in NSCLC have plateaued. Accordingly, sizeable efforts have gone into developing novel therapies. Tumor angiogenesis mediated principally by VEGF has emerged as an alluring target because of its vital role in tumor growth, sustenance and metastasis. The Eastern Cooperative Oncology Group (ECOG) trial E4599 showed significant improvement in overall survival with addition of bevacizumab, a VEGF monoclonal antibody, to cytotoxic chemotherapy in metastatic NSCLC. A number of compounds targeting tumor angiogenesis have since gone into preclinical and clinical testing. The multifaceted nature of cancer has led to development of multitarget tyrosine kinase inhibitors (MTKIs) that target several pathways concomitantly. Motesanib, an orally administered potent small molecule, targets VEGFR 1 â€" 3, PDGFR and KIT. Oral bioavailability and preliminary evidence of activity make this compound an appealing choice for additional investigations. Areas covered: This review summarizes the background of angiogenesis and rationale for targeting the VEGF pathway in NSCLC. The authors also review recent clinical trial data evaluating motesanib. Expert opinion: VEGF is a validated target in NSCLC. In early trials motesanib has shown promising activity in NSCLC with tolerable toxicity profile. A Phase III trial with motesanib in combination with chemotherapy is ongoing.
AB - Introduction: Benefits from conventional chemotherapy in NSCLC have plateaued. Accordingly, sizeable efforts have gone into developing novel therapies. Tumor angiogenesis mediated principally by VEGF has emerged as an alluring target because of its vital role in tumor growth, sustenance and metastasis. The Eastern Cooperative Oncology Group (ECOG) trial E4599 showed significant improvement in overall survival with addition of bevacizumab, a VEGF monoclonal antibody, to cytotoxic chemotherapy in metastatic NSCLC. A number of compounds targeting tumor angiogenesis have since gone into preclinical and clinical testing. The multifaceted nature of cancer has led to development of multitarget tyrosine kinase inhibitors (MTKIs) that target several pathways concomitantly. Motesanib, an orally administered potent small molecule, targets VEGFR 1 â€" 3, PDGFR and KIT. Oral bioavailability and preliminary evidence of activity make this compound an appealing choice for additional investigations. Areas covered: This review summarizes the background of angiogenesis and rationale for targeting the VEGF pathway in NSCLC. The authors also review recent clinical trial data evaluating motesanib. Expert opinion: VEGF is a validated target in NSCLC. In early trials motesanib has shown promising activity in NSCLC with tolerable toxicity profile. A Phase III trial with motesanib in combination with chemotherapy is ongoing.
KW - MTKI
KW - NSCLC
KW - VEGF
KW - angiogenesis
KW - motesanib
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U2 - 10.1517/13543784.2011.579103
DO - 10.1517/13543784.2011.579103
M3 - Article
C2 - 21534718
AN - SCOPUS:79955827262
SN - 1354-3784
VL - 20
SP - 859
EP - 869
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 6
ER -