Resumen de Sequential RAS mutations evaluation in cell‑free DNA of patients with tissue RAS wild‑type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study
Manuel Valladares Ayerbes, María José Safont, E. González Flores, Pilar García Alfonso, Enrique Aranda Aguilar, Ana María López Muñoz, Esther Falcó Ferrer, Lluís Cirera Nogueras, Nuria Rodríguez Salas, Jorge Aparicio Urtasun, Marta Llanos Muñoz, Paola Patricia Pimentel Cáceres, Oscar Alfredo Castillo Trujillo, María del Rosario Vidal Tocino, Mercedes Salgado Fernández, Antonieta Salud, Bartomeu Massuti Sureda, Rocío García Carbonero, María Ángeles Vicente Conesa, Ariadna Lloansí
Purpose RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution.
Methods/patients PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression.
Results 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch).
Conclusions The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.
