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Eficacia de la inhibición de MEK en pacientes con neoplasias histiocíticas
Eli L Diamond1,2, Benjamin H Durham3,4, Gary A Ulaner2,5
1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|March 15, 2019
Resumen
Las neoplasias histiocíticas dependen de la señalización MAPK. Un ensayo con cobimetinib (un inhibidor de MEK) mostró altas tasas de respuesta en pacientes con y sin mutaciones de BRAF, ofreciendo una nueva terapia para todos los tipos de histiocitosis.
Área de la Ciencia:
- En el campo de la oncología
- Hematología
- Biología molecular
Sus antecedentes:
- Las neoplasias histiocíticas son diversos trastornos hematopoyéticos clonales.
- Las mutaciones en la vía de la proteína quinasa activada por mitógeno (MAPK) son comunes.
- Existe una terapia dirigida para las mutaciones BRAF V600, pero no para otras mutaciones.
Objetivo del estudio:
- Para investigar la dependencia de ERK en las neoplasias histiocíticas.
- Evaluar la eficacia de cobimetinib (un inhibidor de MEK) en pacientes con histiocitosis, independientemente del genotipo del tumor.
- Caracterizar las alteraciones de la vía MAPK en pacientes tratados.
Principales métodos:
- Un ensayo clínico de prueba de concepto con cobimetinib.
- Inscripción de pacientes con histiocitosis independientemente del genotipo del tumor.
- Caracterización paralela de las alteraciones de MAPK para la capacidad de activación de ERK.
Principales resultados:
- Se observó una tasa de respuesta global del 89% en 18 pacientes tratados.
- Las respuestas fueron duraderas, con un 100% en curso a un año y un 94% de supervivencia libre de progresión.
- Cobimetinib fue eficaz en varias mutaciones de la vía MAPK (ARAF, BRAF, RAF1, NRAS, KRAS, MEK1, MEK2).
Conclusiones:
- Las neoplasias histiocíticas muestran una dependencia significativa de la señalización MAPK.
- La inhibición de la MEK con cobimetinib es una estrategia de tratamiento eficaz para todo el espectro de neoplasias histiocíticas.
- Este estudio amplía el beneficio de la terapia molecularmente dirigida a todos los pacientes con histiocitosis.
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