RAS Status in ctDNA After Chemotherapy Among Patients With RAS-Mutant Colorectal Cancer

Results from the RASMEX Study

At the 2023 World Congress on Gastrointestinal Cancers, Shinichi Nishina, MD, Kurashiki Central Hospital, Kurashiki, Japan, presented results from the RASMEX study evaluating the frequency of patients with RAS-mutant metastatic colorectal cancer with no detectable RAS mutation in ctDNA following chemotherapy.

Dr Nishina concluded, “Among patients with RAS-mutant colorectal cancer who respond to first- or second-line chemotherapy, 22.8% of patients had no RAS mutation in ctDNA.”

Transcript:

I'm Shinichi Nishina from the Kurashiki Central Cancer Hospital in Japan. On behalf of the investigators, I present the results of the RASMEX study which evaluates the RAS status in ctDNA after chemotherapy in RAS-mutant metastatic colorectal cancer.

Several studies have shown that colorectal cancer tissue had heterogeneity of gene profiling and the DNA analysis of ctDNA in blood samples could detect the change of gene alteration. Our previous study demonstrated that nearly half of the patients with RAS-mutant metastatic colorectal cancer had no detectable RAS mutations. There have been few studies to prospectively evaluate the RAS status in ctDNA after chemotherapy.

This observational study aimed to evaluate the frequency of patients without RAS mutation and the mutation allele frequency of RAS mutation in ctDNA. The primary endpoint was the frequency of patients with no RAS mutation in ctDNA. We expect that 1 patient with no RAS mutation is detected in 100 patients, at minimum. Thus, the sample size of 300 patients is set for our study.

Blood samples are collected after the registration to measure RAS gene status in ctDNA using liquid biopsy. Key inclusion criteria were tissue RAS-mutant metastatic colorectal cancer, age of 20 or more, ECOG performance status of 0 to 2, histologically confirmed adenocarcinoma, refractory or intolerable after response to first- or second-line chemotherapy.

A total of 300 patients were enrolled in this study, but 241 patients met the inclusion criteria. The median age was 68 years old. There were 71.4% patients with left-sided primary tumor, [and] 62.2% patients were registered after first-line chemotherapy. The primary endpoint, which was the proportion of patient with no RAS mutation in ctDNA, was 22.8%. Subgroup analysis indicated that the frequency is 20% in first-line chemotherapy and 27.5% after second-line chemotherapy.

We analyzed the frequency of patients with no RAS mutation in ctDNA according to metastatic site. The proportion of no RAS-mutant patients with lung or multiple metastatic sites were approximately 10%. The proportion of patients with lung, lymph node, and disseminated metastases were approximately 50%. We also analyzed the frequency of patients with no RAS mutation according to mutation site. The proportion of minor RAS-mutation negative was 43.9%.

In summary, among patients with RAS-mutant colorectal cancer who respond to first- or second-line chemotherapy, 22.8% of patients had no RAS mutation in ctDNA. In patients with lung, lymph node, or peritoneal metastasis only, the proportion of RAS-mutant negative in ctDNA was numerically high. The proportion of patients with minor RAS-mutation is higher compared to KRAS Exon 2 mutation. In conclusion, our prospective trial revealed a proportion of patients had no RAS mutation in ctDNA after first- or second-line chemotherapy. Thank you for your attention.

Source:

Nishina S, Izawa N, Watabe M, et al. RAS status in circulating-tumor DNA after chemotherapy in RAS-mutant mCRC: The RASMEX study (JACCRO CC-17). Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-30