Clinico-pathologic correlates of BRAF mutation status in 207 consecutive patients with metastatic melanoma.

8548 Background: Drugs selectively targeting oncogenic mutant (mut) BRAF show activity against metastatic melanoma (MM) carrying these mutations. Distinguishing clinico-pathologic features of mut BRAF MM may influence patient (pt) selection and stratification in trials of these drugs, but no large studies have comprehensively examined this possibility. Our aim was to identify clinico-pathologic correlates of the BRAF mutation status in pts with MM. Methods: Consecutive BRAF tested pts with MM were followed prospectively. Tumor sections were screened by high resolution melt curve analysis of BRAF exon 15 and abnormal results confirmed by DNA sequencing. Data were collected on demographics, details of the primary melanoma (PM) and diagnostic, prognostic and treatment details from date of first distant metastasis (DM). Chi-square and Mann Whitney U tests were used to assess the association of clinico-pathologic features with BRAF status. Multivariate analysis was performed using a logistic regression model. Results: 97/207 pts (47%) had a mutation in exon 15 of the BRAF gene. Of these 72 (74%) were V600E, 19 (20%) V600K, and 6(6%) another mutation or combination. Pt age at diagnosis of DM was significantly different for mut (median age 56, n = 73) and wt (median age 62, n = 81: p < 0.005) tumours. There was no difference between mut/wt in disease free interval from diagnosis of PM to date of DM, sex, site of metastases at diagnosis of DM, regional lymph node involvement ever, resection of DM with intent to cure, response to chemotherapy (CT) or length of response to CT. ECOG status was not significantly different between mut/wt when adjusted for age. Features of the PM significantly associated (p < 0.05) with BRAF mut were: age at PM ≤ 50 yrs (OR = 3.16, 95%CI: 1.28-7.80); superficial spreading or nodular histopathologic subtype (OR = 3.96, 95%CI: 1.32-11.86); and truncal location (OR = 2.66, 95%CI: 1.09-6.47). Conclusions: The BRAF mutation rate in an Australian MM cohort was 47% and non-V600E activating mutations were more common than previously reported. Characteristics of the preceding PM and age at diagnosis differed in BRAF mut and wt MM pts. Clinical features of metastatic disease were essentially indistinguishable. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline, Roche