Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study
Por:
Díaz-Rubio E., Gómez-España A., Massutí B., Sastre J., Reboredo M., Manzano J.L., Rivera F., Safont M.J., Montagut C., González E., Benavides M., Marcuello E., Cervantes A., Martínez de Prado P., Fernández-Martos C., Arrivi A., Bando I., Aranda E., Aranda E., Gómez A., Massutí B., Yuste A., Rubio E.D., Sastre J., Valladares M., Abad A., Rivera F., Safont M.J., Gallén M., González E., Benavides M., Marcuello E., Tobeña M., Cervantes A., Martínez de Prado P., Fernández-Martos C., Arrivi A., López-Ladrón A., Lacasta A., Llanos M., Remón J., Anton A., Vicent J.M., Galán A., Dueñas R., Tabernero J.M., Manzano H., Gómez M.J., Alfaro J., Losa F., Escudero P., García T., García López J.L., García de Paredes M.L., Velasco A., Almenar D., Vera R., García Puche J.L., Carrato A., Lescure A.R., Jiménez E., Alberola V., García-Foncillas J., Constenla M., Ruiz A., Bueso P., Cabrera E., del Río L., Ponce J., Oltra A., Checa T., Etxeberría A., Alonso C.
Publicada:
1 ene 2012
Resumen:
Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18-2.64). Conclusions/Significance: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses. © 2012 Díaz-Rubio et al.
Filiaciones:
Díaz-Rubio E.:
Department of Medical Oncology, Hospital Clínico San Carlos (HCSC), Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0021), Facultad de Medicina, Uni. Complutense, Instituto de Investigacion Sanitaria del HCSC (IdISSC), Madrid, Spain
Gómez-España A.:
Department of Medical Oncology, Hospital Reina Sofía, Córdoba, Spain
Massutí B.:
Department of Medical Oncology, Hospital General, Alicante, Spain
Sastre J.:
Department of Medical Oncology, Hospital Clínico San Carlos (HCSC), Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0021), Facultad de Medicina, Uni. Complutense, Instituto de Investigacion Sanitaria del HCSC (IdISSC), Madrid, Spain
Reboredo M.:
Department of Medical Oncology, Complejo Hospitalario Universitario La Coruña, La Coruña, Spain
Manzano J.L.:
Department of Medical Oncology, Instituto Catalán de Oncología, Hospital Germans Trias I Pujol, Badalona, Spain
Rivera F.:
Department of Medical Oncology, Hospital Marqués de Valdecilla, Santander, Spain
Safont M.J.:
Department of Medical Oncology, Hospital General de Valencia, Valencia, Spain
Montagut C.:
Department of Medical Oncology, Hospital del Mar, Barcelona, Spain
González E.:
Department of Medical Oncology, Hospital Virgen de las Nieves, Granada, Spain
Benavides M.:
Department of Medical Oncology, Hospital Universitario Carlos Haya, Málaga, Spain
Marcuello E.:
Department of Medical Oncology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
Cervantes A.:
Department of Medical Oncology, Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain
Martínez de Prado P.:
Department of Medical Oncology, Hospital de Basurto, Vizcaya, Spain
Fernández-Martos C.:
Department of Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain
Arrivi A.:
Department of Medical Oncology, Fundación Hospital Son Llatzer, Palma de Mallorca, Spain
Bando I.:
Department of Medical Oncology, Hospital Clínico San Carlos (HCSC), Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0021), Facultad de Medicina, Uni. Complutense, Instituto de Investigacion Sanitaria del HCSC (IdISSC), Madrid, Spain
Aranda E.:
Department of Medical Oncology, Hospital Reina Sofía, Córdoba, Spain
Aranda E.:
Department of Medical Oncology, Hospital Reina Sofía, Córdoba, Spain
Gómez A.:
H. Reina Sofía, Spain
Massutí B.:
Department of Medical Oncology, Hospital General, Alicante, Spain
Yuste A.:
H. General Universitario de Alicante, Spain
Rubio E.D.:
H. Universitario Clínico San Carlos, Spain
Sastre J.:
Department of Medical Oncology, Hospital Clínico San Carlos (HCSC), Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0021), Facultad de Medicina, Uni. Complutense, Instituto de Investigacion Sanitaria del HCSC (IdISSC), Madrid, Spain
Valladares M.:
C. H. Universitario La Coruña, Spain
Abad A.:
ICO. H. Germans Trias i Pujol, Spain
Rivera F.:
Department of Medical Oncology, Hospital Marqués de Valdecilla, Santander, Spain
Safont M.J.:
Department of Medical Oncology, Hospital General de Valencia, Valencia, Spain
Gallén M.:
H. del Mar, Spain
González E.:
Department of Medical Oncology, Hospital Virgen de las Nieves, Granada, Spain
Benavides M.:
Department of Medical Oncology, Hospital Universitario Carlos Haya, Málaga, Spain
Marcuello E.:
Department of Medical Oncology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
Tobeña M.:
H. Santa Creu i Sant Pau, Spain
Cervantes A.:
Department of Medical Oncology, Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain
Martínez de Prado P.:
Department of Medical Oncology, Hospital de Basurto, Vizcaya, Spain
Fernández-Martos C.:
Department of Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain
Arrivi A.:
Department of Medical Oncology, Fundación Hospital Son Llatzer, Palma de Mallorca, Spain
López-Ladrón A.:
H. Nuestra Señora de Valme, Spain
Lacasta A.:
H. de Donostia, Spain
Llanos M.:
H. Universitario de Canarias, Spain
Remón J.:
H. de Mataró, Spain
Anton A.:
H. Miguel Servet, Spain
Vicent J.M.:
H. de Sagunto, Spain
Galán A.:
H. de Sagunto, Spain
Dueñas R.:
H. Ciudad de Jaén, Spain
Tabernero J.M.:
H. Universitari Vall d'Hebrón, Spain
Manzano H.:
H. Son Dureta, Spain
Gómez M.J.:
H. Puerta del Mar, Spain
Alfaro J.:
C. Sanitari de Terrasa, Spain
Losa F.:
H. General de L'Hospitalet, Spain
Escudero P.:
H. C. Universitario Lozano Blesa, Spain
García T.:
H. Morales Meseguer, Spain
García López J.L.:
H. Ramón y Cajal, Spain
García de Paredes M.L.:
H. Ramón y Cajal, Spain
Velasco A.:
H. Universitario de la Princesa, Spain
Almenar D.:
H. Dr. Peset, Spain
Vera R.:
H. de Navarra, Spain
García Puche J.L.:
H. Clínico San Cecilio, Spain
Carrato A.:
H. General Universitario de Elche, Spain
Lescure A.R.:
H. General Universitario de Elche, Spain
Jiménez E.:
H. Jerez de la Frontera, Spain
Alberola V.:
H. Arnau de Vilanova, Spain
García-Foncillas J.:
C. Universitaria de Navarra, Spain
Constenla M.:
Complejo Hospitalario Pontevedra, Spain
Ruiz A.:
H. de Fuenlabrada, Spain
Bueso P.:
H. de Barbastro, Spain
Cabrera E.:
H. Virgen de los Lirios, Spain
del Río L.:
H. Virgen de los Lirios, Spain
Ponce J.:
H. Virgen de los Lirios, Spain
Oltra A.:
H. Virgen de los Lirios, Spain
Checa T.:
I. de Oncología Corachán, Spain
Etxeberría A.:
Instituto Oncológico, Spain
Alonso C.:
H. General de Albacete, Spain
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