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

Cancers

Anna Maria Rachiglio¹  Nicola Normanno¹  Raffaella Pasquale¹  Cristin Roma¹  Laura Forgione¹  Alberto Zaniboni²  Armando Orlandi³  Carlo Antonio Barone³  Giampaolo Tortora³  Evaristo Maiello⁴  Tiziana Latiano⁴  Salvatore Pisconti⁵  Sara Lonardi⁶  Roberto Bordonaro⁷  Lorenzo Antonuzzo⁸  Carmine Pinto⁹  Angela Damato⁹  Antonino Cassata^1,10  Giovanni Luca Frassineti^1,11  Gerardo Rosati^1,12  Francesca Di Fabio^1,13  Giuseppe Tonini^1,14  Daris Ferrari^1,15  Stefano Tamberi^1,16 

[1] Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, 80131 Naples, Italy;Fondazione Poliambulanza, 25124 Brescia, Italy;Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy;IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy;Medical Oncology Division, S. Giuseppe Moscati Hospital, 74010 Taranto, Italy;Medical Oncology IOV, 35128 Padua, Italy;Medical Oncology Unit, ARNAS Garibaldi, 95122 Catania, Italy;Medical Oncology Unit, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy;Medical Oncology Unit, Clinical Cancer Center, AUSL-IRCCS Reggio Emilia, 42122 Reggio Emilia, Italy;Medical Oncology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, 80131 Naples, Italy;Medical Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy;Medical Oncology Unit, Ospedale San Carlo, 85100 Potenza, Italy;Medical Oncology Unit, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy;Medical Oncology Unit, Università Campus Bio-Medico, 00128 Rome, Italy;Ospedale S. Paolo, 20142 Milan, Italy;Ospedale per Gli Infermi, 48018 Faenza, Italy;

关键词: metastatic colorectal cancer;    liquid biopsy;    cell-free DNA;    anti-EGFR therapy;   

DOI  :  10.3390/cancers14041052

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown