Treatment Landscape and Sequencing Challenges in Refractory Non-MSI-High Metastatic Colorectal Cancer

Anwaar Saeed, MD, and Daniel Ahn, MD, open this OncLive Insights program with an overview of the current treatment landscape for patients with non-MSI-high metastatic colorectal cancer who have progressed on standard chemotherapy, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Dr. Ahn reviews the three FDA-approved options available in this setting: regorafenib, trifluridine-tipiracil with or without bevacizumab, and fruquintinib, noting that while each represents a meaningful addition, clinical benefit remains modest across all three. The discussants examine the practical challenges of sequencing these agents, including the limited applicability of sunlight trial data to bevacizumab-exposed populations in the United States, the cytopenia burden associated with trifluridine-tipiracil in heavily pretreated individuals, and the toxicity profile of regorafenib. Dr. Saeed and Dr. Ahn also address how clinicians should frame treatment goals with patients, emphasizing disease stabilization over tumor reduction in this setting.