Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer.
Menée à partir d'échantillons tumoraux et d'échantillons plasmatiques prélevés sur 146 patients atteints d'un cancer colorectal métastatique, cette étude évalue, dans le cadre d'une identification des patients pouvant bénéficier d'une thérapie ciblée anti-EGFR, la concordance entre les résultats de deux méthodes de détection par PCR de mutations du gène RAS, l'une à partir de l'ADN tumoral circulant et l'autre à partir de l'ADN extrait du tissu tumoral
Background: Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-EGFR therapy.
Patients and methods: A prospective-retrospective cohort study was performed. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue.
Results: ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80, 95%CI, 0.71-0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83, 95%CI 0.74-0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases, RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. 48% of the patients showed mutant allele fractions in plasma below 1%.
Conclusions: Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.
Annals of Oncology , résumé, 2016