Table 2.

Targeted therapies for colorectal cancer.

Target	Targeted Agent	Status	Indications and Usage/Study Title
VEGF	Bevacizumab	Approved by FDA	Used to treat metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy as a first- or second-line treatment. Used to treat metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy as a second-line treatment in patients whose cancer progressed when placed on a first-line bevacizumab product-containing regimen.
	Ziv-aflibercept	Approved by FDA	Used to treat metastatic colorectal cancer that is resistant to, or has progressed, when treated with an oxaliplatin-containing regimen in combination with FOLFIRI.
	Ramucirumab	Approved by FDA	Used to treat metastatic colorectal cancer when the disease has progressed during or after prior therapy with bevacizumab, oxaliplatin, and fluoropyrimidine, in combination with FOLFIRI.
EGFR	Cetuximab	Approved by FDA	Used to treat K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer, as determined using an FDA-approved test. Used in combination with FOLFIRI as a first-line treatment. Used in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy. Used as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy, or who are intolerant to irinotecan.
	Panitumumab	Approved by FDA	Used to treat wild-type RAS (defined as wild-type in both KRAS and NRAS, as determined using an FDA-approved test for this use) metastatic colorectal cancer. Used in combination with FOLFOX as a first-line treatment. Used as a monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and an irinotecan-containing chemotherapy. Limitations of use include the fact that it is not recommended for the treatment of patients with RAS-mutant metastatic colorectal cancer, or for whom RAS mutation status is unknown.
BRAF	Encorafenib	Approved by FDA	Used to treat metastatic colorectal cancer with a BRAF V600E mutation, in combination with cetuximab, after prior therapy. Limitations of use include the fact that it is not recommended for the treatment of patients with wild-type BRAF colorectal cancer.
	Vemurafenib	Phase I	A Phase I Study on the Tolerance and Safety of Vemurafenib Film-coated Tablets and a Cetuximab Solution for the Infusion and Camrelizumab Protocol (VCC) concerning the After Line Therapy for BRAF V600E Mutation/MSS Metastatic Colorectal Cancer (NCT05019534).
		Phase II	Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT): A Single-arm Study (NCT03727763).
TβRI	Galunisertib (LY2157299)	Phase I/II	Phase I/II Study concerning Galunisertib Combined With Capecitabine in Patients With Advanced Chemotherapy-Resistant Colorectal Cancer With Peritoneal Metastases (NCT05700656).
	PF-03446962	Phase I	Phase Ib Study concerning the Combination of Regorafenib With PF-03446962 in Patients With Refractory Metastatic Colorectal Cancer (REGAL-1 Trial) (NCT02116894).
HER2	Tucatinib with Trastuzumab	Approved by FDA	Used to treat RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
MET	Cabozantinib	Phase II	A Phase II Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer (NCT04963283).