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Abstract
The treatment of metastatic colorectal cancer has evolved greatly in the last 15 years, involving combined chemotherapy protocols and, in more recent times, new biologic agents. Clinical benefit from the use of targeted therapy with bevacizumab, aflibercept, cetuximab, panitumumab and regorafenib in the treatment of metastatic colorectal cancer is now well established with median overall survival accepted as over 24 months, and with super selection for extended RAS patients higher again. The optimal timing of treatment options requires careful consideration of predictive biomarkers, and importantly the potential for interactions, to derive the maximal benefit. A group of colorectal subspecialty medical oncologists from Australia, the USA, the Netherlands and Germany met during ECCO 2013 to discuss current practice. Subsequent new data from the American Society of Clinical Oncology were also reviewed. This article reviews the evidence discussed in support of modern treatments for colorectal cancer and the decision-making behind the treatment choices, with their benefits and risks.
Financial & competing interests disclosure
The Australian authors have received honoraria and travel support to attend national and international meetings for colorectal cancer from Merck Serono, Amgen, Roche and Sanofi Aventis. Disclosures for the international faculty are as follows: Punt CJA, advisor for Roche, Merck, Amgen, Bayer, Sanofi, Nordic Pharma; Dirk Arnold Research Funding Roche; Daniel Haller Consultant/honoraria, Sanofi-Aventis, Amgen, Genentech; Research funding Roche. The group meeting that enabled the material for this review to be assembled was supported by an unrestricted educational grant from Roche provided to the ‘Adelaide Colorectal Tumour Group’, which facilitated the meeting. Roche did not participate in data compilation or in the writing or viewing the submitted review. The corresponding author has had full access to all the data, warrants that all information has been reviewed and accepted by all participants. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Key issues
Survival for patients with advanced colorectal cancer is now consistently reported to be over 24 months.
The treatment algorithm for advanced colorectal cancer should include early molecular assessment and a decision on the potential for resection of metastasis, and this will form the basis of best use and sequence of available agents.
Super selection for extended RAS wild-type patients sees median overall survival to be closer to 30 months, and 5-year survival consistently over 10%.
The outcome of CALGB 80405 is seen as potentially changing practice if the extended RAS results confirm a survival advantage of upfront anti-EGFR therapy and these results awaited in Q3 of 2014 are eagerly awaited.
New agents such as aflibercept (second line), regorafenib and TAS-102 (latter lines) are now likely to be considered part of standard practice.
There remains the need to define the best use of anti-VEGF therapy with as yet, no defined predictive markers for this class.
Patients who harbor a BRAF mutation continue to have a terrible outlook with median survivals still reported to be less than 12 months in a number of studies. New combinations targeting multiple pathways plus or minus chemotherapy are ongoing.
The future appears to be ‘liquid biopsy’ with the ability to assess predictive markers and acquired mutations without repeated tissue biopsy a major positive.