Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status

American Society of Clinical Oncology
Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status
Eric Van Cutsem, Claus-Henning Köhne, István Láng, Gunnar Folprecht, Marek P. Nowacki, Stefano Cascinu, Igor Shchepotin, Joan Maurel, David Cunningham, Sabine Tejpar, Michael Schlichting, Angela Zubel, Ilhan Celik, Philippe Rougier and Fortunato Ciardiello

+ Author Affiliations

From the University Hospital Gasthuisberg, Leuven, Belgium; Klinikum Oldenburg, Oldenburg; University Hospital Carl Gustav Carus, Dresden; Merck KGaA, Darmstadt, Germany; National Institute of Oncology, Budapest, Hungary; MSC Memorial Cancer Center, Warsaw, Poland; Università Politecnica delle Marche, Ancona; Second University of Naples, Naples, Italy; National Cancer Institute, Kiev, Ukraine; Hospital Clínic, Barcelona, Spain; The Royal Marsden National Health Services Foundation Trust, London, United Kingdom; and the University of Versailles St Quentin, Hôpital Européen Georges Pompidou, Paris, France.


↵Corresponding author: Eric Van Cutsem, MD, PhD, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium; e-mail: eric.vancutsem@uz.kuleuven.ac.be.



Abstract
Purpose
The addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken.

Patients and Methods
Patients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series.

Results
The ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P = .0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P = .0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P < .001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis.

Conclusion
The addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.

Received October 30, 2010.
Accepted February 8, 2011.

Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status




ONCOLOGÍA
Actualidad Ultimas noticias - JANOes y agencias -
Cetuximab mejora en 3,5 meses la supervivencia global en cáncer colorrectal metastásico
JANO.es y agencias · 28 Abril 2011 11:12

.Un análisis actualizado del estudio Crystal, realizado con este anticuerpo monoclonal de Merck Serono. se publica en el “Journal of Clinical Oncology”.


El uso en primera línea de cetuximab, fármaco comercializado por Merck Serono como Erbitux, permite aumentar unos 3,5 meses de media la supervivencia global de los pacientes con cáncer colorrectal metastásico que presentan la mutación KRAS, en comparación con aquellos tratados solamente con la quimioterapia convencional.

Así se desprende de los resultados de un análisis actualizado del estudio fase III Crystal, con un total de 1.198 pacientes, que publica en su último número el Journal of Clinical Oncology.

En concreto, se ha observado que la mediana de supervivencia global en los pacientes que recibieron quimioterapia “Folfiri” más cetuximab fue de 23,5 meses, en comparación con los 20 meses de los que recibieron solo quimioterapia. El riesgo de progresión de la enfermedad, asimismo, se redujo en un 30,4%.

Según ha destacado el investigador principal del estudio y oncólogo del Hospital Universitario Gasthuisberg de Lovaina (Bélgica), Eric van Cutsem, resulta alentador comprobar que este tratamiento combinado “no sólo ofrece una mejora en la tasa de respuesta, sino también una mejora en la supervivencia global”.



JCO 2011, doi: 10.1200/JCO.2010.33.5091
Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status

Erbitux (cetuximab)
Head and Neck Cancer | Colorectal Cancer | ERBITUX (cetuximab)

Journal of Clinical Oncology
Journal of Clinical Oncology

Merck Serono
Merck Serono S.A. - Home.

Actualidad Ultimas noticias - JANOes y agencias - Cetuximab mejora en 35 meses la supervivencia global en cancer colorrectal metastasico - JANO.es - ELSEVIER