RT Journal Article
T1 Optimization of RAS/BRAF Mutational Analysis Confirms Improvement in Patient Selection for Clinical Benefit to Anti-EGFR Treatment in Metastatic Colorectal Cancer.
A1 Santos, Cristina
A1 Azuara, Daniel
A1 Garcia-Carbonero, Rocio
A1 Alfonso, Pilar Garcia
A1 Carrato, Alfredo
A1 Elez, Mª Elena
A1 Gomez, Auxiliadora
A1 Losa, Ferran
A1 Montagut, Clara
A1 Massuti, Bartomeu
A1 Navarro, Valenti
A1 Varela, Mar
A1 Lopez-Doriga, Adriana
A1 Moreno, Victor
A1 Valladares, Manuel
A1 Manzano, Jose Luis
A1 Vieitez, Jose Maria
A1 Aranda, Enrique
A1 Sanjuan, Xavier
A1 Tabernero, Josep
A1 Capella, Gabriel
A1 Salazar, Ramon
AB In metastatic colorectal cancer (mCRC), recent studies have shown the importance to accurately quantify low-abundance mutations of the RAS pathway because anti-EGFR therapy may depend on certain mutation thresholds. We aimed to evaluate the added predictive value of an extended RAS panel testing using two commercial assays and a highly sensitive and quantitative digital PCR (dPCR). Tumor samples from 583 mCRC patients treated with anti-EGFR- (n = 255) or bevacizumab- (n = 328) based therapies from several clinical trials and retrospective series from the TTD/RTICC Spanish network were analyzed by cobas, therascreen, and dPCR. We evaluated concordance between techniques using the Cohen kappa index. Response rate, progression-free survival (PFS), and overall survival (OS) were correlated to the mutational status and the mutant allele fraction (MAF). Concordance between techniques was high when analyzing RAS and BRAF (Cohen kappa index around 0.75). We observed an inverse correlation between MAF and response in the anti-EGFR cohort (P < 0.001). Likelihood ratio analysis showed that a fraction of 1% or higher of any mutated alleles offered the best predictive value. PFS and OS were significantly longer in RAS/BRAF wild-type patients, independently of the technique. However, the predictability of both PFS and OS were higher when we considered a threshold of 1% in the RAS scenario (HR ¼ 1.53; CI 95%, 1.12–2.09 for PFS, and HR ¼ 1.9; CI 95%, 1.33–2.72 for OS). Although the rate of mutations observed among techniques is different, RAS and BRAF mutational analysis improved prediction of response to anti-EGFR therapy. Additionally, dPCR with a threshold of 1% out performed the other platforms.
PB American Association for Cancer Research
YR 2017
FD 2017-06-06
LK http://hdl.handle.net/10668/11311
UL http://hdl.handle.net/10668/11311
LA en
NO Santos C, Azuara D, Garcia-Carbonero R, Alfonso PG, Carrato A, Elez ME, et al.  Optimization of RAS/BRAF Mutational Analysis Confirms Improvement in Patient Selection for Clinical Benefit to Anti-EGFR Treatment in Metastatic Colorectal Cancer. Mol Cancer Ther. 2017 Sep;16(9):1999-2007
DS RISalud
RD Apr 15, 2025