Options for metastatic colorectal cancer beyond the second line of treatment

Colorectal cancer is the third most common cancer, with recent advances in the management of unresectable metastatic lesions. The aim of this review is to discuss the remaining options for heavily pretreated patients with unresectable metastatic colorectal cancer. Beyond second-line treatment, two epidermal growth factor receptor (EGFR) inhibitors, cetuximab and panitumumab, have a demonstrated clinical interest in patients with KRAS wild-type tumours. However, few data exist in patients pretreated with an anti-EFGR and who are being rechallenged with anti-EGFR drugs. Reintroduction of chemotherapy should be considered. In September 2012, regorafenib, a multi-kinase inhibitor was approved by the US Federal Drug Administration for patients refractory to other standard treatments. In the case of metastases limited to the liver, transarterial chemoembolization, hepatic artery infusion and radioembolization could also be discussed in selected patients. With the multiplication of therapeutic options in first-line, second-line treatment, and beyond, the concept of subsequent lines of chemotherapy should be replaced by a multiline strategy, dependent on the patient and on tumour biology. A better understanding of the tumour biology and predictive factors for the response to these therapies is needed, and further strategic trials are urgently warranted.