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ESMO 2026 | RAS mutation dynamics and survival in metastatic colorectal cancer
Hiroki Osumi, MD, PhD, Kanagawa Cancer Center, Yokohama, Japan, explores a SCRUM-Japan MONSTAR-SCREEN 1 substudy (UMIN000036749) evaluating RAS mutation dynamics in metastatic colorectal cancer using paired tissue and circulating tumor DNA (ctDNA) next-generation sequencing before and after treatment. Pretreatment tissue and ctDNA RAS status were highly concordant, although ctDNA more frequently detected subclonal mutations. Higher ctDNA variant allele frequency independently predicted shorter progression-free survival, while conversion from RAS-mutant to wild-type, seen only in patients with subclonal mutations, was associated with longer progression-free survival, highlighting potential biomarker utility. This interview took place at the European Society for Medical Oncology (ESMO) 2026 Congress in Madrid, Spain.
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Transcript
the RAS mutation is an important biomarker of the efficacy of anti-EGF therapy, but RAS status sometimes change from mutant to wild-type or wild-typing mutant after the systemic therapy. So three years ago, I present in the R-school meeting. Okay. So the RAS mutation, so from mutant to wild-type, we call the nebulous phenomenon. So some patients initially RAS mutant to, after the following chemotherapy, RAS mutants to wild type...
the RAS mutation is an important biomarker of the efficacy of anti-EGF therapy, but RAS status sometimes change from mutant to wild-type or wild-typing mutant after the systemic therapy. So three years ago, I present in the R-school meeting. Okay. So the RAS mutation, so from mutant to wild-type, we call the nebulous phenomenon. So some patients initially RAS mutant to, after the following chemotherapy, RAS mutants to wild type. The incidence of the, around the 15 to 20%, an interesting rate, these patients are effective for the anti-EGF therapy that is initially effective, I think. Okay. So, but the limitation of the, our previous study is that, so pre-treatment ctDNA status is unknown. So to overcome this limitation, we use data from the Scrum Japan MonsterOne study that is an nationwide genomic program that evaluates the pre – treatment paired ct DNA and tissue samples, and after the treatment, ctDNA sample is in the data. So we evaluated concordance rate of the pre-treatment tissue and ct DNA sample and the RAS dynamics, relationship with RAS-DAT dynamics and survival in this study. So the main result is that concordant rate of tissue and CTDNA samples. of the RAS test was higher than 93 percent, and it’s very interesting that the RAs mutants are really frequency of the ct DNA is lower, significantly lower than the tissue samples. And also sub-coronary mutation in the cTD, RAS mutation in ct DNA is higher than the tissue samples, and yes. Okay. So it’s most importantly these paired concordance cases, RAS neurosis phenomenon has occurred in around 20%. That means that from originally RAS mutant to the, after the treatments, a wild type. And yes, after a few patients, initially RAS wild type to the RAS mutants. Okay. But their prognosis is very short. And the opposite RAS mutant to RAS wild type, their prognosis is very long. And based on these results, I think we have to be checked, RAS or other alteration status, when do we change the treatments for the, yes, longitudinally as to optimize treatment sequences in the future direction of the treatment. Yes. So we have to change the treatment strategy and metastatic corrective cancer.
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