Background: Vemurafenib (VEM), a BRAF kinase inhibitor, has demonstrated high response rates and improved progression-free and overall survival in pts with BRAF^V600mutation–positive metastatic melanoma (mM). We present interim results from predefined subgroups from a large multicenter, open-label safety study of VEM in pts with mM (NCT01307397). Methods: Pts with BRAF^V600mutation–positive histologically confirmed mM received VEM (960 mg BID) as first-line therapy or subsequent to previous therapies. Assessments for safety and efficacy were made every 28 days. Results: As of Feb 29, 2012, 2,265 pts have received VEM. Pts had a median age of 54.0 (13-95) yrs and median time since diagnosis of mM of 6.2 (0-351.9) mos. 59% had received prior systemic therapy. Median time of exposure to VEM as of the cut-off date was 3 (0.03-11.24) mos for the overall population and majority of subgroups, and approximately 2.5 mos for pts with ECOG ≥2 and age ≥75 yrs. 1537 (68%) pts were still receiving VEM at the cut-off date. 728 (32%) pts discontinued, most frequently because of PD (538/728 pts; 74%). Adverse events (AEs) were reported for 87% of all patients, with arthralgia (32%) and rash (26%) the most frequent. The incidences of AEs in the subgroups are summarized (Table). Although efficacy analyses are limited by the short duration of follow-up, six-month OS rate was 76% (95% CI 72-79%) and median PFS was 4.1 mos (95% CI 3.9-4.5 mos). Postbaseline tumor assessments were available for 63% and 30% of pts at wk 8 and 16, respectively. At wk 8 CR: 2%, PR: 57%, SD: 30%, PD: 6%. At wk 16 CR: 3%, PR: 46%, SD: 31%, PD: 15%. Conclusions: Although the overall safety profile of VEM in this study was consistent with previous clinical data, interim analyses of subgroups suggest that very elderly pts may be at higher risk of G3 AEs. Clinical trial information: NCT01307397.