Optimizing biologic sequencing in metastatic colorectal cancer: first line and beyond

Abstract

Significant advances in the treatment of metastatic colorectal cancer (mcrc) since the early 2000s have led to improved clinical outcomes, including overall survival (os). When fluorouracil was the sole treatment agent for mcrc, os in phase iii studies was approximately 12 months. Now, in 2019, the median os (mos) in the most recent mcrc clinical trials has been approaching 3 years. The biologic agents that target the vascular endothelial growth factor (vegf), epithelial growth factor receptor (egfr), human epidermal growth factor receptor 2 (her2), PD-1, ctla-4, ntrk, and braf pathways play important roles in the mcrc treatment algorithm, given their significant-sometimes dramatic-activity. Emerging data indicate that the choice of a specific biologic at a particular time (line of treatment) for specific patient populations (based on tumour characteristics) is critical. In the present review, we discuss the available evidence for optimal biologic sequencing in the management of mcrc.

Keywords: Colorectal cancer; biologics; treatments.

FIGURE 1

(A) Simplified consideration for choosing biologics. (B) Biologics for specific patient populations. mCRC = metastatic colorectal cancer; EGFR = epidermal growth factor receptor; pMMR = proficient mismatch repair; dMMR = deficient mismatch repair; MSI-H = high microsatellite instability; HER2 = human epidermal growth factor receptor 2; FOLFOXIRI = fluorouracil–leucovorin–oxaliplatin–irinotecan.