Updates in the Treatment of Metastatic Colorectal Cancer

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Midhun Malla
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Katrina S. Pedersen
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Aparna R. Parikh
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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.

Disclosures: Dr. Malla has disclosed receiving consulting fees from AstraZeneca Pharmaceuticals LP, Exelixis Inc., and Natera. Dr. Pedersen has disclosed receiving grant/research support from Arcus Biosciences, BioLineRx, Boston Biomedical, Bristol-Myers Squibb Company, Daiichi-Sankyo Co., Genentech, Inc., HCW Biologics, Incyte Corporation, Ipsen, MedImmune Inc., Merck & Co., Inc., Natera, Nouscome, Novartis Pharmaceuticals Corporation, Pierre-Fabre, Pfizer Inc., Rafael Pharmaceuticals, Inc., and Roche Laboratories, Inc.; and serving as a scientific advisor for AstraZeneca Pharmaceuticals LP, Pfizer Inc., GlaxoSmithKline, Novartis Pharmaceuticals Corporation, SAGA Diagnostics, and Taiho Pharmaceuticals Co., Ltd. Dr. Parikh has disclosed receiving consulting fees from AbbVie, Inc., Bayer HealthCare, Checkmate Pharmaceuticals, CVS, Delcath Systems, Inc., Eli Lilly and Company, Foundation Medicine, Pfizer Inc., Saga Laboratories, Seagen, Scare Therapeutics, Taiho Pharmaceuticals Co., Ltd., and Value Analytics Laboratory; receiving grant/research support from Bristol-Myers Squibb Company, Daiichi-Sankyo Co., Erasca, Inc., Genentech, Inc., Mirati Therapeutics Inc., Novartis Pharmaceuticals Corporation, PMV Pharmaceuticals, PureTech Health, and Taiho Pharmaceuticals Co., Ltd.; owning equity interest/stock options in C2I Genomics, Parithera, and XGenomes; serving as a scientific advisor for Karkinos; and receiving royalty income from UpToDate.

Correspondence: Midhun Malla, MD, MS, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26508. Email: midhun.malla@hsc.wvu.edu;

Katrina S. Pedersen, MD, MS, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO 63110. Email: kpedersen@wustl.edu; and

Aparna R. Parikh, MD, MS, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA 02114. Email: aparna.parikh@mgh.harvard.edu
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