Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies

Giampaolo Tortora, Carlo Antonio Barone, Alberto Zaniboni, Armando Orlandi, Anna Maria Rachiglio, Laura Forgione, Raffaella Pasquale, Evaristo Maiello, Lorenzo Antonuzzo, Antonino Cassata, Giuseppe Tonini, Roberto Bordonaro, Gerardo Rosati, Sara Lonardi, Daris Ferrari, Giovanni Luca Frassineti, Stefano Tamberi, Salvatore Pisconti, Francesca Di Fabio, Cristin RomaTiziana Latiano, Angela Damato, Carmine Pinto, Nicola Normanno

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)1052-N/A
RivistaCancers
Volume14
DOI
Stato di pubblicazionePubblicato - 2022

Keywords

  • Anti-EGFR therapy
  • Metastatic colorectal cancer
  • Liquid biopsy
  • Cell-free DNA

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