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Thématique :
- Cancer colorectal (CCR)
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Pas encore
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Nom du veilleur :
Professeur David TOUGERON
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Annals of oncology
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2018/01
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2018 Jan;29(1):112-118.
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doi: 10.1093/annonc/mdx417.
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RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial
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Normanno N, Esposito Abate R, Lambiase M, Forgione L, Cardone C, Iannaccone A, Sacco A, Rachiglio AM, Martinelli E, Rizzi D, Pisconti S, Biglietto M, Bordonaro R, Troiani T, Latiano TP, Giuliani F, Leo S, Rinaldi A, Maiello E, Ciardiello F; CAPRI-GOIM Investigators.
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https://www.ncbi.nlm.nih.gov/pubmed/28950295
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Abstract
BACKGROUND:
Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy.
PATIENTS AND METHODS:
In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing.
RESULTS:
A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis.
CONCLUSION:
This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.
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Le statut RAS est indispensable pour définir la stratégie de traitement des cancers colorectaux métastatiques. Il est habituellement analysé sur la tumeur mais des études ont montré qu’il pouvait être déterminé à partir de l’ADN tumoral circulant. Dans cet essai la valeur prédictive de réponse au traitement du statut RAS (efficacité des anti-EGFR) a été comparée entre la tumeur et le sang circulant.
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La concordance du statut RAS entre la tumeur et le sang circulant n’était que de 78,3%, la plupart des discordances s’expliquant par la sensibilité des techniques de biologie moléculaire (taux d’allèles mutés inférieurs à 1% non détectables par certaines techniques). Les mutations RAS qu’elles soient détectées dans la tumeur ou le sang circulant étaient fortement prédictives de la résistance aux anti-EGFR.
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Ces résultats confirment que le statut RAS peut être évalué à partir du sang circulant dans les cancers colorectaux métastatiques, notamment en cas d’accès difficile aux prélèvements tumoraux. Des études en cours devront permettre de valider que l’apparition de mutations RAS dans le sang circulant, sous traitement ou avant la ré-introduction d’anti-EGFR, doivent être recherchée systématiquement car prédictive de la résistance au traitement.
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