Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti-Epidermal Growth Factor Receptor Therapy.

Autor:	Maurel J; Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Alonso V; Hospital Universitario Miguel Servet, Zaragoza, Spain., Escudero P; Hospital Universitario Lozano Blesa, Zaragoza, Spain., Fernández-Martos C; Fundación Instituto Valenciano de Oncologia, Valencia, Spain., Salud A; Hospital Universitari Arnau de Vilanova, Lleida, Spain., Méndez M; Hospital de Móstoles, Móstoles, Spain., Gallego J; Hospital General Universitario of Elche, Elche, Spai., Rodriguez JR; Hospital Infanta Cristina, Badajoz, Spain., Martín-Richard M; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Fernández-Plana J; Hospital Mutua de Terrasa, Terrasa, Spain., Manzano H; Hospital Son Espases, Palma, Spain., Méndez JC; Centro Oncologico de Galicia, A Coruña, Spain., Zanui M; Hospital de Mataró, Mataró, Spain., Falcó E; Hospital Son Llàtzer, Palma, Spain., Gil-Raga M; Hospital de Sagunto, Sagunto, Spain., Aparicio J; Hospital La Fe de Valencia, Valencia, Spain., Feliu J; Hospital Universitario La Paz, Madrid, Spain., García-Albéniz X; Harvard School of Public Health, Boston, MA., Torres F; Hospital Cliníc, Barcelona, Spain., Rojo F; Hospital Fundación Jimenez Diaz, Madrid, Spain., Bellosillo B; Hospital del Mar Medical Research Institute, Barcelona, Spain., Mendiola M; Hospital Universitario La Paz, Madrid, Spain., Fernández V; Hospital Cliníc, Barcelona, Spain., Reig O; Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Claes B; Biocartis, Mechelen, Belgium., Maertens G; Biocartis, Mechelen, Belgium., Sablon E; Biocartis, Mechelen, Belgium., Jacobs B; Biocartis, Mechelen, Belgium., Montagut C; Hospital del Mar Medical Research Institute, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2019 Dec; Vol. 3, pp. 1-16.
DOI:	10.1200/PO.18.00289
Abstrakt:	Purpose: RAS and BRAF mutations can be detected as a mechanism of acquired resistance in circulating tumor (ct) DNA in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor therapy. Methods: RAS and BRAF mutational status was assessed in ctDNA in a baseline plasma sample and a serum sample collected at the time of the last available determination (named secondary extraction) from patients with KRAS exon 2 wild-type metastatic colorectal cancer treated in two first-line prospective biomarker-designed clinical trials (PULSE, ClinicalTrials.gov identifier: NCT01288339; and POSIBA, ClincialTrials.gov identifier: NCT01276379). Results: Analysis of extended RAS and BRAF in tissue and plasma from 178 patients with KRAS exon 2 wild-type metastatic colorectal cancer showed a sensitivity of 64.1% and a specificity of 90%. The median overall survival (OS) of baseline patients with RAS and BRAF mutations in ctDNA was 22.3 months (95% CI, 15.6 to 29 months) and 8.9 months (95% CI, 6.3 to 11.4 months), respectively, which was significantly inferior to the median OS of 40.4 months (95% CI, 35.9 to 44.9 months) in two patients with wild-type disease ( P < .001). Acquisition of RAS/BRAF mutations occurred in nine of 63 patients (14%) with progressive disease (PD; ie, blood draw within 1 month before PD or after PD) compared with six of 73 patients (8%) with no PD or blood extraction for ctDNA analysis before 1 month of PD ( P = .47). Median OS in patients with RAS/BRAF acquisition was 23.9 months (95% CI, 19.7 to 27.9 months) compared with 40.6 months (95% CI, not reached to not reached) in patients who remained free of mutations ( P = .016). Conclusion: Our results confirm that baseline RAS and BRAF testing in ctDNA discriminates survival. The emergence of RAS/BRAF mutations has limited relevance for the time to progression to anti-epidermal growth factor receptor therapy.
Databáze:	MEDLINE
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