Navigating later lines of treatment for advanced colorectal cancer - optimizing targeted biological therapies to improve outcomes

Sharlene Gill; Scot Dowden; Bruce Colwell; Loretta L Collins; Scott Berry

doi:10.1016/j.ctrv.2014.10.002

Navigating later lines of treatment for advanced colorectal cancer - optimizing targeted biological therapies to improve outcomes

Cancer Treat Rev. 2014 Dec;40(10):1171-81. doi: 10.1016/j.ctrv.2014.10.002. Epub 2014 Oct 16.

Authors

Sharlene Gill¹, Scot Dowden², Bruce Colwell³, Loretta L Collins⁴, Scott Berry⁵

Affiliations

¹ British Columbia Cancer Agency, Division of Medical Oncology, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada. Electronic address: [email protected].
² Tom Baker Cancer Centre, Department of Medical Oncology, 1331 - 29th Street NW, Calgary, AB T2N 4N2, Canada. Electronic address: [email protected].
³ QEII Health Sciences Centre, Medical Oncology, 1276 South Park St, Halifax, NS B3H 2Y9, Canada. Electronic address: [email protected].
⁴ Kaleidoscope Strategic, 146 Marion Street, Toronto, ON M6R 1E7, Canada. Electronic address: [email protected].
⁵ Sunnybrook Odette Cancer Centre, Medical Oncology, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada. Electronic address: [email protected].

PMID: 25458604
DOI: 10.1016/j.ctrv.2014.10.002

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer among males and second among females worldwide. The treatment landscape for advanced CRC (aCRC) is rapidly evolving and there are now a number of randomized trials assessing treatment of aCRC beyond first-line, prompting important questions about how to optimize therapy and maximize benefit. The availability of targeted agents has increased the complexity of post-progression treatment of aCRC. Targeted biological agents with varying modes of action are now approved for use in second-line and beyond, including the VEGF-inhibitors bevacizumab and aflibercept, the VEGFR/multikinase-inhibitor regorafenib, and the EGFR-inhibitors cetuximab and panitumumab. This article provides a systematic overview of the available phase III trial data, discusses biomarkers predictive of response to treatment, addresses safety concerns associated with specific agents, and provides practical, evidence-based recommendations for the later lines of treatment for patients with unresectable aCRC.

Keywords: Chemorefractory; EGFR-inhibitor; Second-line; Targeted therapy; Third-line; VEGF-inhibitor.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antibodies, Monoclonal / pharmacology
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized / pharmacology
Antibodies, Monoclonal, Humanized / therapeutic use
Antineoplastic Agents / adverse effects
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Bevacizumab
Biomarkers, Tumor / analysis
Cetuximab
Clinical Trials, Phase III as Topic
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / metabolism*
Humans
Molecular Targeted Therapy
Panitumumab
Phenylurea Compounds / pharmacology
Phenylurea Compounds / therapeutic use
Pyridines / pharmacology
Pyridines / therapeutic use
Receptors, Vascular Endothelial Growth Factor / pharmacology
Receptors, Vascular Endothelial Growth Factor / therapeutic use
Recombinant Fusion Proteins / pharmacology
Recombinant Fusion Proteins / therapeutic use
Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Biomarkers, Tumor
Phenylurea Compounds
Pyridines
Recombinant Fusion Proteins
VEGFA protein, human
Vascular Endothelial Growth Factor A
aflibercept
regorafenib
Bevacizumab
Panitumumab
Receptors, Vascular Endothelial Growth Factor
Cetuximab