Molecular testing for BRAF V600 mutations in the BRIM-2 trial of the BRAF inhibitor vemurafenib in metastatic melanoma.

10523 Background: The BRAF inhibitor vemurafenib (V) has shown dramatic activity in early clinical trials in patients with BRAFV600 mutation-positive melanoma. Preclinical and Phase 1 clinical data show the drug has minimal activity in tumors lacking BRAF mutations, creating a need for an accurate diagnostic test to identify appropriate patients for therapy. Methods: To assess eligibility for BRIM-2, a Phase 2 trial of V in patients with BRAFV600 mutation-positive metastatic melanoma, tumor samples were screened with an investigational PCR assay (cobas 4800 BRAF V600 Mutation Test) designed to detect the canonical V600E (1799T>A) mutation. 328 samples were tested of which 327 samples gave valid results. BRAF mutations were detected in 184 (56.3 %); 132 patients with BRAF-mutation positive melanoma were enrolled into the trial based on clinical eligibility criteria. Sanger sequencing was performed retrospectively on DNA samples from all enrolled patients. Results: Fifteen samples (11.4%) gave invalid Sange...