Plasma Dynamics of RAS/RAF Mutations in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy and Anti-EGFR Treatment

Caroline Brenner Thomsen*, Rikke Fredslund Andersen, Jan Lindebjerg, Torben Frøstrup Hansen, Lars Henrik Jensen, Anders Jakobsen

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Resumé

BACKGROUND: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment.

PATIENTS AND METHODS: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR.

RESULTS: Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0).

CONCLUSION: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC.

OriginalsprogEngelsk
TidsskriftClinical Colorectal Cancer
Vol/bind18
Udgave nummer1
Sider (fra-til)28-33.e3
ISSN1533-0028
DOI
StatusUdgivet - mar. 2019

Fingeraftryk

Colorectal Neoplasms
Mutation
Neoplasms
DNA
Precision Medicine
Polymerase Chain Reaction

Citer dette

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title = "Plasma Dynamics of RAS/RAF Mutations in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy and Anti-EGFR Treatment",
abstract = "BACKGROUND: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment.PATIENTS AND METHODS: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR.RESULTS: Forty-six patients were prospectively enrolled onto the study. At baseline, 7{\%} had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22{\%}. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0).CONCLUSION: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC.",
keywords = "Biomarkers, ctDNA, Liquid biopsy, Precision medicine, Targeted therapy, Proto-Oncogene Proteins B-raf/blood, Prognosis, Prospective Studies, Follow-Up Studies, Biomarkers, Tumor/blood, Humans, Middle Aged, Male, ErbB Receptors/antagonists & inhibitors, ras Proteins/blood, DNA, Neoplasm/blood, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Colorectal Neoplasms/blood, Liver Neoplasms/blood, Female, Aged, Mutation",
author = "Thomsen, {Caroline Brenner} and Andersen, {Rikke Fredslund} and Jan Lindebjerg and Hansen, {Torben Fr{\o}strup} and Jensen, {Lars Henrik} and Anders Jakobsen",
year = "2019",
month = "3",
doi = "10.1016/j.clcc.2018.10.004",
language = "English",
volume = "18",
pages = "28--33.e3",
journal = "Clinical Colorectal Cancer",
issn = "1533-0028",
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TY - JOUR

T1 - Plasma Dynamics of RAS/RAF Mutations in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy and Anti-EGFR Treatment

AU - Thomsen, Caroline Brenner

AU - Andersen, Rikke Fredslund

AU - Lindebjerg, Jan

AU - Hansen, Torben Frøstrup

AU - Jensen, Lars Henrik

AU - Jakobsen, Anders

PY - 2019/3

Y1 - 2019/3

N2 - BACKGROUND: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment.PATIENTS AND METHODS: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR.RESULTS: Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0).CONCLUSION: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC.

AB - BACKGROUND: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment.PATIENTS AND METHODS: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR.RESULTS: Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0).CONCLUSION: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC.

KW - Biomarkers

KW - ctDNA

KW - Liquid biopsy

KW - Precision medicine

KW - Targeted therapy

KW - Proto-Oncogene Proteins B-raf/blood

KW - Prognosis

KW - Prospective Studies

KW - Follow-Up Studies

KW - Biomarkers, Tumor/blood

KW - Humans

KW - Middle Aged

KW - Male

KW - ErbB Receptors/antagonists & inhibitors

KW - ras Proteins/blood

KW - DNA, Neoplasm/blood

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Colorectal Neoplasms/blood

KW - Liver Neoplasms/blood

KW - Female

KW - Aged

KW - Mutation

U2 - 10.1016/j.clcc.2018.10.004

DO - 10.1016/j.clcc.2018.10.004

M3 - Journal article

VL - 18

SP - 28-33.e3

JO - Clinical Colorectal Cancer

JF - Clinical Colorectal Cancer

SN - 1533-0028

IS - 1

ER -