Antibodies for Treatment of Metastatic Colorectal Cancer
Substantial progress has been achieved in the treatment of metastatic colorectal cancer (mCRC) during the last two decades and overall survival (OS) has been prolonged from 12 months to more than 30 months in recent studies (Table 9.1) [1]. This major ste
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Antibodies for Treatment of Metastatic Colorectal Cancer Volker Heinemann and Sebastian Stintzing
Introduction Substantial progress has been achieved in the treatment of metastatic colorectal cancer (mCRC) during the last two decades and overall survival (OS) has been prolonged from 12 months to more than 30 months in recent studies (Table 9.1) [1]. This major step towards increased treatment efficacy was made possible not only by the introduction of new chemotherapeutic agents such as irinotecan and oxaliplatin, but also by the availability of targeted agents directed against the epidermal growth factor receptor (EGFR) as well as against the vascular endothelial growth factor (VEGF).
The EGFR Pathway The EGFR constitutes the link between the extracellular space and the intracellular signal transduction, which regulates nuclear processes involved in cell growth, differentiation, survival, cell cycle progression, angiogenesis, and drug sensitivity. It is a member of the erbB family of receptor tyrosine kinases, which also include erbB2 (HER2), erbB3 (HER3), and erbB4 (HER4). The EGFR- transmembrane protein is composed of three components: an extracellular ligand-binding domain, a lipophilic transmembrane domain, and an intracellular tyrosine kinase domain. Apart from erbB2, specific ligands have been identified for each of the erbB receptors. Among these, the epidermal growth factor (EGF) and the transforming growth factor-α (TGF-α) selectively bind to the EGFR. Extracellular ligand binding induces activation of the transmembrane receptors, subsequent homo- or heterodimerisation between the V. Heinemann, MD (*) • S. Stintzing Department of Hematology and Oncology, Klinikum der Universität München, Marchionini-Strasse 15, 81377 Munich, Germany e-mail: [email protected] © Springer International Publishing Switzerland 2017 D. Kerr, R. Johnson (eds.), Immunotherapy for Gastrointestinal Cancer, DOI 10.1007/978-3-319-43063-8_9
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[8]
[20]
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[1]
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[77]
OPUS
PRIME
COINa
NORDICa
FIRE-3
CALGB 80405
PEAK
Regimen FOLFIRI + Cet FOLFIRI FOLFOX + Cet FOLFOX FOLFOX + Pani FOLFOX FU/LV or Cape + Ox FU/LV or Capeb + Ox + Cet FLOX FLOX + Cet FOLFIRI + Cet FOLFIRI + Bev FOLFOX/FOLFIRI + Cet FOLFOX/FOLFIRI + Bev FOLFOX + Pani FOLFOX + Bev
Legend: aPatients with KRAS wild-type tumours b 67 % Cape-based therapy
Refs. [6]
Study CRYSTAL
No of patients 178 189 38 49 259 253 367 362 97 97 199 201 270 256 88 82
ORR (%) 66.3 38.6 58 29 60 47 57 64 47 46 65.3 58.7 68.6 53.8 63.6 60.5 NR
1.75 (
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