Estado del arte con el tratamiento con inhibidores de BRAF + MEK

Vemurafenib

Fase I (BRIM-1)→

Flaherty KT,

et al.

N Engl J Med 2010

Escalada de dosis

55 pacientes con tumores sólidos

• 49 melanoma metastásico

• 3 cáncer papilar tiroides

• 3 otros cánceres

Vemurafenib 160–1120 mg/12 horas p.o.

Objetivos

• Seguridad y fármacocinetica

• DMT

• Respuestas, SLP

960 mg/12 horas p.o. recomendada fase II

Fase extensión

32 pacientes melanoma metastásico

Mutación BRAF V600E

Objetivos

Respuestas

Toxicidad, fármacodinamia, PK

Figure 2. Representative Findings of the Effect of PLX4032 at the Recommended Phase 2 Dose

in Study Patients with Melanoma That Carried the V600E Mutation

The recommended phase 2 dose was 960 mg twice daily. Panel A (hematoxylin and eosin)

shows immunohisto-chemical analyses of the expression of phosphorylated extracellular

signal-regulated kinase (ERK), cyclin D1, and Ki-67 in tumor-biopsy specimens obtained at

baseline and on day 15 of treatment. Panel B shows the uptake of

F-fluorodeoxyglucose

(FDG) at baseline and on day 15 of treatment, as assessed by means of positron-emission

tomography (PET). Panel C shows computed tomographic images of lesions (arrows) in

lung, liver, and bone (with each pair of images shown for a different patient) at baseline and

at 8 weeks.

Flaherty et al.

Page 11

N Engl J Med

. Author manuscript; available in PMC 2013 July 26.

NIH-PA Author Manuscript

81% respuestas

Mediana SLP > 7 meses

SG 2 años→ 38% (ESMO 2011)

SG 3 años→ 26% (SMR 2012)