Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer.

Abstract

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-epidermal growth factor receptor (EGFR) therapy.

PATIENTS AND METHODS:

A prospective-retrospective cohort study was carried out. 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. Forty-eight percent 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.

• Authors: J Grasselli, E Elez, G Caratù, J Matito, C Santos, T Macarulla, J Vidal, M Garcia, J M Viéitez, D Paéz, E Falcó, C Lopez Lopez, E Aranda, F Jones, V Sikri, P Nuciforo, R Fasani, J Tabernero, C Montagut, D Azuara, R Dienstmann, R Salazar, A Vivancos
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 28 Issue 6 Pg. 1294-1301 (Jun 01 2017) ISSN: 1569-8041 [Electronic] England
• PMID: 28368441 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• ErbB Receptors

Topics

• Colorectal Neoplasms (blood, drug therapy, genetics, pathology)
• ErbB Receptors (antagonists & inhibitors)
• Genes, ras
• Humans
• Mutation
• Neoplasm Metastasis