Prognostic Value of the Combination of Circulating Tumor Cells Plus KRAS in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab |
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| Authors: | Javier Sastre Marta Vidaurreta Auxiliadora Gómez Fernando Rivera Bartomeu Massutí Margarita Reboredo López Albert Abad Manuel Gallen Manuel Benavides Enrique Aranda Eduardo Díaz Rubio |
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| Affiliation: | 1. Medical Oncology Department, HC San Carlos, Madrid, Spain (Center affiliated with the Red Temática de Investigación Cooperativa (RD06/0020/0021), Instituto Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain);2. Central Laboratory Department, HC San Carlos, Madrid, Spain;3. Medical Oncology Department, Hospital Reina Sofía, Córdoba, Spain;4. Medical Oncology Department, Hospital Marqués de Valdecilla, Santander, Spain;5. Medical Oncology Department, Hospital Universitario de Alicante, Alicante, Spain;6. Medical Oncology Department, Hospital Universitario de A Coruña, A Coruña, Spain;7. Medical Oncology Department, Hospital Germans Trias i Pujol, Badalona, Spain;8. Medical Oncology Department, Hospital del Mar, Barcelona, Spain;9. Medical Oncology Department, Hospital Carlos Haya, Málaga, Spain;1. Department of Hematology, University Hospital Virgen del Rocío/IBIS/CSIC/University of Seville, Seville, Spain;2. Department of Hematology, University Hospital of Salamanca, Salamanca, Spain;1. Department of Oncology, Parc Taulí Sabadell Hospital Universitari, Sabadell, Barcelona, Spain;2. Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain;3. Department of Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;4. Department of Medical Oncology, Hospital Clínico Universitario, Santiago de Compostela, A Coruña, Spain;5. Department of Medical Oncology, Hospital del Mar-IMAS, Barcelona, Spain;1. Department of Animal Medicine and Surgery, University of Córdoba, Córdoba, Spain;1. Unit of HIV/Hepatitis coinfection, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;2. Infectious Diseases-HIV Unit Hospital General Universitario “Gregorio Marañón”, Madrid, Spain;3. Pathology Department, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain;4. Internal Medicine Department, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain;5. Microbiology Department, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain;1. Servicio de Endocrinología y Nutrición, Hospital Universitario Central de Asturias, Oviedo, Asturias, España;2. Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, Oviedo, Asturias, España;1. CHUV – Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;2. Vall d''Hebron University Hospital, Barcelona, Spain;3. Hospital Clinico Universitario de Valencia, Valencia, Spain;4. The Royal Marsden Hospital (Chelsea) – NHS Foundation Trust, London, UK;5. The Clatterbridge Cancer Centre, Liverpool, UK;6. Universitätsklinikum Leipzig – Universitäres Krebszentrum Leipzig, Leipzig, Germany |
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| Abstract: | ![]()
ObjectiveCirculating tumor cells (CTCs) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) status were identified as prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab in analyses of the MACRO (Maintenance Treatment in Advanced Colorectal Cancer) trial. In this post hoc analysis of the MACRO trial, the potential additive effect of these 2 factors on patient outcomes was explored.MethodsA total of 158 of the 480 patients involved in the MACRO trial were included in the biological marker substudy. CTC isolation and enumeration were centralized and performed using the CellSearch System (Veridex LLC, Raritan, NJ) in 7.5 mL of whole blood. Evaluation of KRAS status was performed retrospectively by the standard method used at each center. PFS and OS were analyzed by the Kaplan–Meier method according to CTC count and KRAS status.ResultsPatients with < 3 CTC per 7.5 mL blood at baseline and KRAS wild-type tumors had a median PFS of 14.2 months compared with 6.2 months in patients with ≥ 3 CTCs and KRAS mutated tumors (P < .0001; hazard ratio, 3.0; 95% confidence interval, 1.8-5.2). Similar findings were observed for OS (28.9 and 13.7 months, respectively, P = .0004; hazard ratio 2.8; 95% confidence interval, 1.6-4.9). Multivariate analyses showed that CTC count ≥ 3 and KRAS status were the only independent prognostic factors for both PFS and OS.ConclusionsThis post hoc analysis showed that CTC count and KRAS status were independent prognostic factors for outcomes in patients with metastatic colorectal cancer treated with bevacizumab ± chemotherapy. These factors should be taken into account in the design of future phase III trials. |
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| Keywords: | Bevacizumab Capecitabine Circulating tumor cells Colorectal cancer Oxaliplatin Prognostic factors |
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