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.