title: Navigating later lines of treatment for advanced colorectal cancer - optimizing targeted biological therapies to improve outcomes.
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.
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada. Electronic address: sgill@bccancer.bc.ca.
authors.forename: Sharlene
authors.initials: S
authors.lastname: Gill
authors.affiliation: Tom Baker Cancer Centre, Department of Medical Oncology, 1331 - 29th Street NW, Calgary, AB T2N 4N2, Canada. Electronic address: Scot.Dowden@albertahealthservices.ca.
authors.forename: Scot
authors.initials: S
authors.lastname: Dowden
authors.affiliation: QEII Health Sciences Centre, Medical Oncology, 1276 South Park St, Halifax, NS B3H 2Y9, Canada. Electronic address: Bruce.Colwell@cdha.nshealth.ca.
authors.forename: Bruce
authors.initials: B
authors.lastname: Colwell
authors.affiliation: Kaleidoscope Strategic, 146 Marion Street, Toronto, ON M6R 1E7, Canada. Electronic address: Loretta@kstrategic.com.
authors.forename: Loretta L
authors.initials: LL
authors.lastname: Collins
authors.affiliation: Sunnybrook Odette Cancer Centre, Medical Oncology, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada. Electronic address: Scott.Berry@sunnybrook.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Berry
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis; D000068818:Cetuximab; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D000077544:Panitumumab; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000494:pharmacology / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; C559147:regorafenib; D000068258:Bevacizumab; D000077544:Panitumumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000068818:Cetuximab
keywords: Chemorefractory; EGFR-inhibitor; Second-line; Targeted therapy; Third-line; VEGF-inhibitor