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Selecting Optimal First-Line Treatment for Microsatellite Stable and Non-Mutated RAS/BRAF Metastatic Colorectal Cancer

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Opinion statement

Standard frontline treatment of metastatic colorectal cancer (CRC) is cytotoxic chemotherapy plus a biologic agent such as an anti-EGFR monoclonal antibody (cetuximab or panitumumab) or anti-VEGF antibody (bevacizumab). Predictive biomarkers include mismatch repair (MMR) status, and RAS and BRAF mutation status; and important factors in treatment selection include primary tumor location, intent of therapy, and potential toxicity, as well as patient age, comorbidities, and patient preference. To date, single-, double-, or triple-agent cytotoxic chemotherapy all have important roles in appropriately selected patients, with the addition of anti-VEGF or anti-EGFR antibody therapy based on the relevant predictive biomarker. Data indicate that patients with proficient MMR, RAS/BRAF wt mCRC are candidates for an anti-EGFR antibody plus doublet chemotherapy if they have a left-sided primary tumor, or for anti-VEGF (bevacizumab) plus doublet or triplet chemotherapy if they have a right-sided primary tumor. Future studies may provide more predictive biomarkers to further personalize therapy for this heterogeneous disease.

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Authors and Affiliations

  1. Division of Oncology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA

    Oluwadunni E. Emiloju MBBS, MS, Mojun Zhu MD, Hao Xie MD, PhD, Zhaohui Jin MD, Frank A. Sinicrope MD, FACP & Joleen M. Hubbard MD

  2. Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Frank A. Sinicrope MD, FACP

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FAS reports consulting/advisory funds from Guardant Health, Roche/Genentech, and patent-related royalties from Roche Diagnostics. JMH reports advisory funds from Bayer, Merck, BeiGene, Incyte, Taiho; and research funding to institution from Merck, Treos Bio, Senhwa pharmaceuticals, Bayer, Incyte, TriOncology, Seattle Genetics, Hutchison MediPharma, Pionyr Immunotherapeutics, Trovogene, G1 Therapeutics, Roche, Pfizer, Cardiff Oncology, Mirati Therapeutics, Xilis Inc.

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Emiloju, O.E., Zhu, M., Xie, H. et al. Selecting Optimal First-Line Treatment for Microsatellite Stable and Non-Mutated RAS/BRAF Metastatic Colorectal Cancer. Curr. Treat. Options in Oncol. 24, 1739–1757 (2023). https://doi.org/10.1007/s11864-023-01142-8

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