The optimization of second-line therapy for metastatic colorectal cancer: new targeted therapy options

Advances in the treatment of metastatic colorectal cancer (mCRC) during the past years, largely associated with the wide use of targeted agents and effective chemotherapy regimens in routine clinical practice, as well as with the introduction of the "continuum of care" concept. This concept means a clear planning of the treatment sequence and identifying the optimal combination of the chemotherapy regimen and targeted agent at each setting. Following this approach the role of the 2-nd line setting is dramatically icreasing, and this review aimed to identify the best treatment combination for the mCRC patients at this setting. The optimal treatment sequence for most patients with unresectable metastases is the use of oxaliplatin containing regimen the in 1-st line and switch to FOLFIRI (duplet containing irinotecan and infusion of 5-fluorouracil) in the 2-nd line treatment for metastatic colorectal cancer.Therefore, the choice of the most effective targeted agent in combination with FOLFIRI seems extremely actual. Various targeted biological agents including as anti-EGFR antibodies as well as antiangiogenic agents such as bevacizumab and aflibercept have been studied in various combinations in the 2-nd line setting for mCRC treatment.Anti-EGFR antibodies in 2-nd line treatment increased progression-free survival, but didn’t result in the overall survival increase, while angiogenesis inhibitors were effective in terms of PFS and OS in bevacizumab-naive patients as well as in bevacizumab pretreated patients. Aflibercept was the first targeted agent showed the increase of overall survival as well as progression-free survival and objective response rate in 2-line setting when combined with FOLFIRI in a broad population of mCRC patients.