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document
Impact of MET expression on outcome in BRAF ( V600E/K ) advanced melanoma . AIMS Preclinical data suggest that signalling through the HGF-MET pathway may confer resistance to BRAF inhibition in BRAF ( V600E/K ) melanoma . Therefore , blockade of HGF-MET signalling might be a valid therapeutic strategy , in combination with BRAF inhibition , in BRAF ( V600E/K ) melanoma . The aim of this study was to investigate the clinical relevance of these observations by evaluating the survival impact of MET expression in patients with BRAF ( V600E/K ) advanced melanoma treated with vemurafenib . METHODS AND RESULTS Formalin-fixed tissue blocks were obtained of tumours from patients enrolled in the BRIM2 ( n = 59 ) and BRIM3 ( n = 150 ) trials of vemurafenib in advanced BRAF ( V600E/K ) melanoma . Immunohistochemistry for MET ( SP44 rabbit monoclonal antibody ) was performed with a highly validated assay and clinically validated scoring system . Pretreatment MET expression was frequent at the ≥1 + cutoff ( BRIM3 , 31 % ; BRIM2 , 49 % ) , but relatively infrequent at the ≥2 + cutoff ( BRIM3 , 9 % ; BRIM2 , 19 % ) . Retrospective subset analyses showed that , irrespective of the cutoff used or the treatment arm , MET expression did not show prognostic significance , in terms of objective response rate , progression-free survival , or overall survival . CONCLUSIONS MET is expressed in a proportion of BRAF ( V600E/K ) advanced melanomas . Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib-treated melanoma .
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Intervention_Pharmacological
BRAF inhibition
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Intervention_Pharmacological
vemurafenib
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Participant_Condition
advanced melanoma
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Participant_Condition
BRAF ( V600E/K ) advanced melanoma
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Participant_Condition
BRIM2
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Participant_Sample-size
59
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Participant_Condition
BRIM3
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Participant_Sample-size
150