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Updates in the Treatment of Metastatic Colorectal Cancer

Presented by: Midhun Malla, Katrina S. Pedersen, and Aparna R. Parikh

Molecular biomarker testing for all patients with metastatic colorectal cancer (CRC) has become increasingly important because identifying targetable alterations can lead to meaningful clinical benefits. At a minimum, testing should include RAS, BRAF mutational status, microsatellite instability status, HER2 expression, NTRK, and RET mutations. For HER2-amplified cancer, the NCCN Guidelines offer multiple treatment options, including trastuzumab in combination with tucatinib or pertuzumab, and trastuzumab-deruxtecan. Combination trastuzumab + tucatinib has recently received approval by the FDA for refractory RAS wild-type, HER2-amplified CRC. The addition of bevacizumab to trifluridine/tipiracil treatment has significantly prolonged median overall survival compared with trifluridine/tipiracil alone, regardless of molecular subtypes. KRAS G12C–targeted therapies are on the horizon, with several agents in ongoing studies. Furthermore, bilevel blockade is important when addressing MAP kinase pathway alterations.

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Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology

Al B. Benson III, Alan P. Venook, Mohamed Adam, George Chang, Yi-Jen Chen, Kristen K. Ciombor, Stacey A. Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Paul Haste, J. Randolph Hecht, Sarah Hoffe, Steven Hunt, Hisham Hussan, Kimberly L. Johung, Nora Joseph, Natalie Kirilcuk, Smitha Krishnamurthi, Midhun Malla, Jennifer K. Maratt, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, Benjamin Shogan, John M. Skibber, Constantinos T. Sofocleous, Anna Tavakkoli, Christopher G. Willett, Christina Wu, Lisa A. Gurski, Jenna Snedeker, and Frankie Jones

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.