Perioperative Management of Resectable Metastatic Colon Cancer

Introduction to Perioperative Therapy

The National Comprehensive Cancer Network (NCCN) panel explicitly cautions that cetuximab in the perioperative setting may harm patients with resectable metastatic colon cancer 1, 2, 3

The New EPOC trial was stopped early due to protocol-defined futility criteria, indicating that the combination of FOLFIRI plus cetuximab may cause harm and significantly worsen outcomes in patients with resectable metastatic colon cancer 1
Progression-free survival was significantly worse with cetuximab: 14.8 months versus 24.2 months without cetuximab (HR 1.50; 95% CI 1.00-2.25; P<0.048) in the New EPOC trial 1, 2, 3
This represents a nearly 10-month reduction in progression-free survival when cetuximab was added to chemotherapy in the New EPOC trial 1

The NCCN recommends against using FOLFOX plus cetuximab in patients with resectable disease 1, 2, 3
The NCCN recommends using FOLFIRI plus cetuximab with caution in those with unresectable disease that could potentially be converted to resectable status 1, 2, 3

FOLFIRI plus cetuximab has demonstrated efficacy in the first-line metastatic (unresectable) setting for appropriately selected patients with RAS wild-type tumors and left-sided primary tumors 4, 5
In patients with KRAS wild-type metastatic disease, FOLFIRI plus cetuximab showed improved overall survival: 23.5 versus 20.0 months (P=0.009) in the CRYSTAL trial 5, 6
In patients with KRAS wild-type metastatic disease, FOLFIRI plus cetuximab showed improved progression-free survival: 9.9 versus 8.7 months (HR 0.68; 95% CI 0.50-0.94; P=0.02) in the CRYSTAL trial 5, 6

For patients with resectable synchronous liver and/or lung metastases, the NCCN guidelines recommend FOLFOX or CapeOX (preferred) ± bevacizumab 7
For patients with resectable synchronous liver and/or lung metastases, the NCCN guidelines recommend FOLFIRI ± bevacizumab 7
The NCCN guidelines recommend avoiding cetuximab in the perioperative setting for patients with resectable metastatic colon cancer 1, 2, 3