Initial systemic therapy for metastatic colorectal cancer

FOLFIRI: irinotecan plus leucovorin and short-term infusional fluorouracil; FOLFOX: oxaliplatin plus leucovorin and short-term infusional fluorouracil; FOLFOXIRI: infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan; HER2: human epidermal growth factor receptor 2; PS: performance status.

* Use of cetuximab and panitumumab is contraindicated in patients with tumoral RAS mutations or BRAF V600E mutations.

¶ For example, high tumor burden, highly symptomatic disease, initially unresectable but potentially resectable liver metastases.

Δ Contraindications to bevacizumab may include:

• Major surgery within 28 days
• Active bleeding
• Untreated hemorrhagic brain metastases
• Arterial thromboembolic event within the last 6 to 12 months

◊ Backbone chemotherapy doublets appropriate for use with cetuximab or panitumumab include FOLFOX or FOLFIRI. An additional doublet that can be used alone or in combination with bevacizumab is oxaliplatin plus capecitabine (CAPOX/XELOX). FOLFIRI is preferred over an oxaliplatin-containing regimen for patients who received adjuvant oxaliplatin-based chemotherapy within the last 12 months or if there was any oxaliplatin-related neuropathy.

§ Although it is more toxic than doublet therapy, triplet therapy may be preferred for patients with a good PS who are able to tolerate it and who have biologically aggressive/poor-prognosis cancer (eg, right-sided cancer, BRAF V600E mutation, large tumor volume, need for strong response to be eligible for metastasectomy).