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Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations David E. Gerber, MD, Leena Gandhi, MD, PhD, and Daniel B. Costa, MD, PhD

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Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations David E. Gerber, MD, Leena Gandhi, MD, PhD, and Daniel B. Costa, MD, PhD. - PowerPoint PPT Presentation

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Page 1: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Management and Future Directions in Non-Small Cell Lung

Cancer with Known Activating Mutations

David E. Gerber, MD, Leena Gandhi, MD, PhD, and Daniel B. Costa, MD, PhD

Page 2: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

El cáncer de pulmón es un tumor de mal pronóstico a pesar de los avances en el conocimiento de la enfermedad y en la aprobación de nuevos tratamientos.

Representa una cuarta parte de todas las muertes por cáncer.

Page 3: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Esta revisión proporcionará una visión general de los subgrupos moleculares de cáncer de pulmón, incluyendo la descripción de oncogenes (EGFR, ALK, KRAS, ROS1, RET, BRAF, ErbB2, NTRK1, FGFR, entre otros) y cómo estos predicen la respuesta a pequeña inhibidores de la molécula de tirosina quinasa. Ya sea clínicamente disponibles o en desarrollo de ensayos clínicos para NSCLC avanzado.

Prestando particular atención en el subgrupo con EGFR mutado y ALK reorganizado.

El cáncer de pulmón tiene una de las tasas de mutaciones más altas, en comparación con otro tipo de cáncer.

Page 4: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Frecuencia de alteraciones

oncogénicas en pulmón en

carcinoma de células no pequeñas.

Page 5: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Mutaciones EGFR en NSCLC

EGFR es un miembro de la familia ErbB de los receptores transmembrana tirosina quinasas implicados en las vías de transducción de señales que regulan la proliferación y la apoptosis.

La mayoría de los tumores que responden a los TKI de EGFR presentan mutaciones activadoras en el dominio tirosin-kinasa del gen EGFR.

Siendo más frecuentes en mujeres, no fumadores, raza asiática e

histología adenocarcinoma.

Page 6: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Estas mutaciones consisten en pequeñas delecciones en el exón 19 (L747-A750) o sustituciones nucleotídicas que modifican el aminoácido resultante, en los exones 18 (G719C) y 21 (L858R y L861Q).

Page 7: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations
Page 8: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations
Page 9: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Algoritmo propuesto para el manejo clínico de los

resistencia adquirida a los TKI del EGFR gefitinib, erlotinib y afatinib en el CPNM con mutación EGFR

Page 10: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Reordenamiento de EML4-ALK

El oncogén de fusión EML4-ALK fue descripto inicialmente en 2007.

El perfil del paciente con esta mutación es un varón, joven, con ausencia de hábito tabáquico y en particular en adenocarcinomas 3-7%.

Page 11: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

Representative Clinical Trials of Crizotinib (250 mg Twice Daily) and Other ALK Inhibitors for Advanced ALK Rearranged NSCLC

Page 12: Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

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