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Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies
SIMPLE SUMMARY: Increasing evidence suggests that circulating cell-free DNA (cfDNA) testing might allow for monitoring the response to anti-EGFR monoclonal antibodies in patients with metastatic colorectal carcinoma (mCRC). However, few data are available in treatment-naïve patients. We tested cfDNA...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870112/ https://www.ncbi.nlm.nih.gov/pubmed/35205799 http://dx.doi.org/10.3390/cancers14041052 |
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author | Rachiglio, Anna Maria Forgione, Laura Pasquale, Raffaella Barone, Carlo Antonio Maiello, Evaristo Antonuzzo, Lorenzo Cassata, Antonino Tonini, Giuseppe Bordonaro, Roberto Rosati, Gerardo Zaniboni, Alberto Lonardi, Sara Ferrari, Daris Frassineti, Giovanni Luca Tamberi, Stefano Pisconti, Salvatore Di Fabio, Francesca Roma, Cristin Orlandi, Armando Latiano, Tiziana Damato, Angela Tortora, Giampaolo Pinto, Carmine Normanno, Nicola |
author_facet | Rachiglio, Anna Maria Forgione, Laura Pasquale, Raffaella Barone, Carlo Antonio Maiello, Evaristo Antonuzzo, Lorenzo Cassata, Antonino Tonini, Giuseppe Bordonaro, Roberto Rosati, Gerardo Zaniboni, Alberto Lonardi, Sara Ferrari, Daris Frassineti, Giovanni Luca Tamberi, Stefano Pisconti, Salvatore Di Fabio, Francesca Roma, Cristin Orlandi, Armando Latiano, Tiziana Damato, Angela Tortora, Giampaolo Pinto, Carmine Normanno, Nicola |
author_sort | Rachiglio, Anna Maria |
collection | PubMed |
description | SIMPLE SUMMARY: Increasing evidence suggests that circulating cell-free DNA (cfDNA) testing might allow for monitoring the response to anti-EGFR monoclonal antibodies in patients with metastatic colorectal carcinoma (mCRC). However, few data are available in treatment-naïve patients. We tested cfDNA samples obtained from mCRC patients enrolled in a phase III trial of the anti-EGFR monoclonal antibody cetuximab plus chemotherapy as first-line treatment. Analysis of serial plasma samples revealed a complex dynamic of RAS/BRAF mutations in response to treatment, with transitory peaks of these mutations that were not associated with resistance to therapy. Overall, our findings suggest that early appearance of RAS/BRAF mutations in the plasma of patients receiving first-line anti-EGFR agents in combination with chemotherapy should not be considered as marker of resistance. ABSTRACT: Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline (n = 37), at 8 weeks of treatment (n = 32), progressive disease (PD; n = 36) and 3 months after PD (n = 21). cfDNA testing was performed using the Idylla™ ctKRAS and ctNRAS-BRAF tests and the Oncomine Pan-Cancer Cell-Free Assay. Analysis of basal samples revealed RAS/BRAF mutations in 6/37 cases. A transient RAS positivity not associated with PD was observed at 8 weeks in five cases that showed no mutations at baseline and PD. The frequency of mutant cases increased at PD (33.3%) and decreased again at 3 months after PD (9.5%). The median progression-free survival (mPFS) of patients RAS/BRAF mutant at PD was 7.13 months versus 7.71 months in wild-type patients (p = 0.3892). These data confirm that the occurrence of RAS/BRAF mutations in mCRC patients receiving anti-EGFR agents is relatively frequent. However, the cfDNA dynamics of RAS mutations in patients treated with anti-EGFR agents plus polychemotherapy are complex and might not be directly associated with resistance to treatment. |
format | Online Article Text |
id | pubmed-8870112 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88701122022-02-25 Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies Rachiglio, Anna Maria Forgione, Laura Pasquale, Raffaella Barone, Carlo Antonio Maiello, Evaristo Antonuzzo, Lorenzo Cassata, Antonino Tonini, Giuseppe Bordonaro, Roberto Rosati, Gerardo Zaniboni, Alberto Lonardi, Sara Ferrari, Daris Frassineti, Giovanni Luca Tamberi, Stefano Pisconti, Salvatore Di Fabio, Francesca Roma, Cristin Orlandi, Armando Latiano, Tiziana Damato, Angela Tortora, Giampaolo Pinto, Carmine Normanno, Nicola Cancers (Basel) Article SIMPLE SUMMARY: Increasing evidence suggests that circulating cell-free DNA (cfDNA) testing might allow for monitoring the response to anti-EGFR monoclonal antibodies in patients with metastatic colorectal carcinoma (mCRC). However, few data are available in treatment-naïve patients. We tested cfDNA samples obtained from mCRC patients enrolled in a phase III trial of the anti-EGFR monoclonal antibody cetuximab plus chemotherapy as first-line treatment. Analysis of serial plasma samples revealed a complex dynamic of RAS/BRAF mutations in response to treatment, with transitory peaks of these mutations that were not associated with resistance to therapy. Overall, our findings suggest that early appearance of RAS/BRAF mutations in the plasma of patients receiving first-line anti-EGFR agents in combination with chemotherapy should not be considered as marker of resistance. ABSTRACT: Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline (n = 37), at 8 weeks of treatment (n = 32), progressive disease (PD; n = 36) and 3 months after PD (n = 21). cfDNA testing was performed using the Idylla™ ctKRAS and ctNRAS-BRAF tests and the Oncomine Pan-Cancer Cell-Free Assay. Analysis of basal samples revealed RAS/BRAF mutations in 6/37 cases. A transient RAS positivity not associated with PD was observed at 8 weeks in five cases that showed no mutations at baseline and PD. The frequency of mutant cases increased at PD (33.3%) and decreased again at 3 months after PD (9.5%). The median progression-free survival (mPFS) of patients RAS/BRAF mutant at PD was 7.13 months versus 7.71 months in wild-type patients (p = 0.3892). These data confirm that the occurrence of RAS/BRAF mutations in mCRC patients receiving anti-EGFR agents is relatively frequent. However, the cfDNA dynamics of RAS mutations in patients treated with anti-EGFR agents plus polychemotherapy are complex and might not be directly associated with resistance to treatment. MDPI 2022-02-18 /pmc/articles/PMC8870112/ /pubmed/35205799 http://dx.doi.org/10.3390/cancers14041052 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rachiglio, Anna Maria Forgione, Laura Pasquale, Raffaella Barone, Carlo Antonio Maiello, Evaristo Antonuzzo, Lorenzo Cassata, Antonino Tonini, Giuseppe Bordonaro, Roberto Rosati, Gerardo Zaniboni, Alberto Lonardi, Sara Ferrari, Daris Frassineti, Giovanni Luca Tamberi, Stefano Pisconti, Salvatore Di Fabio, Francesca Roma, Cristin Orlandi, Armando Latiano, Tiziana Damato, Angela Tortora, Giampaolo Pinto, Carmine Normanno, Nicola Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies |
title | Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies |
title_full | Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies |
title_fullStr | Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies |
title_full_unstemmed | Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies |
title_short | Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies |
title_sort | dynamics of ras/braf mutations in cfdna from metastatic colorectal carcinoma patients treated with polychemotherapy and anti-egfr monoclonal antibodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870112/ https://www.ncbi.nlm.nih.gov/pubmed/35205799 http://dx.doi.org/10.3390/cancers14041052 |
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