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Study Identifies New Patient Response Biomarker for Colorectal Cancer Therapy

Despite advances in precision cancer medicine, there is still an unmet need for patient selection biomarkers for many chemotherapies. For example, the metastatic colorectal cancer (mCRC) drug cocktail trifluridine/tipiracil (FTD/TPI) offers durable responses in some patients but only a very modest survival benefit in the general mCRC population. To gain insights into why some patients respond well to FTD/TPI and others do not, researchers from the Netherlands Cancer Institute and elsewhere performed a whole-genome analysis of 37 mCRC patients treated with the chemotherapy, identifying KRAS codon G12 mutations as a potential biomarker of resistance. They then examined real-world data for 960 patients with mCRC receiving FTD/TPI, validating that the mutations were significantly associated with poor survival. Data on hundreds of mCRC patients who participated in a global Phase III of FTD/TPI, meanwhile, further established KRAS codon G12 mutations as predictive biomarkers for reduced overall survival benefit of the chemotherapy. The findings, which the researchers report in Nature Medicine, point to KRAS codon G12 mutations as important biomarkers for identifying patients who will respond poorly to FTD/TPI and highlight the power of genomics-based personalized medicine, they write.