KEY TAKEAWAYS
- The study aimed to examine RAS mutation dynamics and their clinical significance in mCRC.
- The study concluded early ctDNA RAS assay use guides EGFR regimen decisions in individuals with RAS-MT mCRC.
In metastatic colorectal cancer (mCRC), RAS mutation loss may occur during the standard-of-care regimen and can lead to resistance to therapy. This phenomenon, known as acquired resistance, is a major challenge in treating mCRC.
Kenta Iguchi and the team aimed to investigate the temporal dynamics of RAS mutations and their clinical significance.
The study included 82 individuals with tissue RAS-mutant (RAS-MT) mCRC who underwent circulating tumor DNA (ctDNA) RAS monitoring between January 2013 and April 2023. The analysis focused on the rate of acquired RAS mutation loss (aRAS-ML) over time and associated clinicopathological factors. The prognostic relevance of mutation loss was also evaluated.
The results revealed that acquired RAS mutation loss (aRAS-ML) was detected in 33 (40.2%) individuals, with 32 experiencing mutation loss in the first ctDNA RAS assay. Those with a RAS mutation in the first assay had a median of 8 months until the second ctDNA RAS assay, with 4.5% newly converting to aRAS-ML; no new conversions were detected at the third assay.
The aRAS-ML group showed a higher incidence of single-organ metastases in the target organ during ctDNA measurement (aRAS-ML: 84.8% vs. RAS-MT: 59.2%, P= 0.02). Among the 33 individuals with aRAS-ML, 7 (21.2%) received anti-epidermal growth factor receptor (EGFR) therapy, with a median progression-free survival of 8 months. Multivariate analysis identified persistent ctDNA RAS mutation as an independent prognostic factor for overall survival (HR: 2.7, 95% CI: 1.1-6.3, P= 0.02).
The study concluded that for patients with RAS-MT metastatic colorectal cancer, the rate of ctDNA mutation loss diminishes over time. Therefore, early utilization of a ctDNA RAS assay during treatment may aid in reevaluating the appropriateness of EGFR regimens.
No funding was received.
Source: https://pubmed.ncbi.nlm.nih.gov/38805050/
Iguchi K, Shiozawa M, Uchiyama M, et al. (2024). “Temporal dynamics of RAS mutations in circulating tumor DNA in metastatic colorectal cancer: clinical significance of mutation loss during treatment.” J Cancer Res Clin Oncol. 2024 May 28;150(5):281. doi: 10.1007/s00432-024-05805-3. PMID: 38805050.
