Current and Emerging Therapies in Refractory Metastatic Colorectal Cancer

John L. Marshall, MD


November 08, 2023

New and emerging therapies for refractory metastatic colorectal cancer (mCRC) continue to move the bar in treatment options, according to Dr John L. Marshall, director of the Ruesch Center for the Cure of Gastrointestinal Cancers in Washington, DC.

Standard first- and second-line treatment approaches for mCRC involve a combination of chemotherapies and biologics that can generate 1-2 years of disease control. But metastatic disease becomes refractory to commonly used drugs such as oxaliplatin, irinotecan, and anti-EGFR monoclonal antibodies.

Among the earliest treatment options in the refractory space was the oral multi-kinase inhibitor regorafenib. Dr Marshall discusses how clinicians managed the drug's toxicity through dosing, making it a go-to for patients with refractory disease.

A trial of the fixed-dose combination medication trifluridine-tipiracil (TAS-102) mirrored the progression-free survival data seen with regorafenib.

A subsequent trial found that treatment with TAS-102 plus bevacizumab resulted in longer overall survival than TAS-102 alone.

The tyrosine kinase inhibitor fruquintinib is pending FDA approval. An oral VEGF inhibitor, fruquintinib targets all three of the VEGF receptors.

Dr Marshall closes by discussing emerging targeted therapies and combination immunotherapy approaches that promise further clinical benefit for patients with metastatic disease.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.