1125P - Open-Label Pilot Study of Vemurafenib in Previously Treated Metastatic Melanoma (MM) Patients (PTS) with Symptomatic Brain Metastases (BM)

Abstract

ABSTRACT Background The BRAF inhibitor vemurafenib has shown high response rates and improved progression-free and overall survival in mM harbouring V600-mutated BRAF. BMs are often observed with mM and indicate a poor prognosis. The aim of this preliminary investigation is to determine the feasibility of vemurafenib therapy in mM with BM. Methods 24 evaluable pts with BRAFV600 mutation positive (cobas® 4800 BRAF V600 Mutation Test) mM and BMs, requiring corticosteroids for symptom control, were enrolled (Nov 2010–Nov 2011). Pts received twice-daily vemurafenib 960 mg. Primary endpoint is safety; secondary endpoint is best overall response rate (RECIST v1.1). Results All pts were white, median age 47 (24–70) years. Median baseline number of BMs was 3.5 (1–20). Median time since BM diagnosis was 3.2 (0–64) months. Other lesion sites included skin, lung, liver, bone, lymph nodes, colon/large intestine, stomach, breast and adrenal. All pts had prior treatment for BM: radiotherapy 83% (58% whole brain, 25% precision), 2 pts had surgery and 83% of pts had systemic therapy. As of clinical data cut-off (15 Dec 2011), median treatment duration was 117 (3–304) days. 9 pts are ongoing; 15 (63%) discontinued treatment because of progression of disease (PD), 8 of whom died because of PD. 22 pts (92%) reported ≥1 adverse event (AE), which were mainly mild or moderate. Most common AEs were arthralgia (33%), photosensitivity (21%) and seizures (20%, pre-existing). 3 pts reported 1 of each of the following grade 3 AEs: epilepsy, cutaneous squamous cell carcinoma (cuSCC), increased amylase, elevated γ-glutamyltransferase and ileus with perforation. Overall, cuSCC occurred in 3 pts (12.5%), skin papilloma in 3 pts (12.5%) and keratoacanthoma in 1 pt (4.2%). 7/24 pts (29%) had a confirmed partial response: 9 pts (38%) had stable disease, 3 (12%) PD and 5 (21%) were not evaluable for response. Median duration of response was 3.8 (0.8–4.7) months. Conclusions Vemurafenib therapy is feasible in advanced melanoma patients with symptomatic BM. Interpretation of efficacy is currently limited because of a short follow-up time, but there are strong indications of vemurafenib activity in BM. Disclosure R. Dummer: Research funding: Astra Zeneca, Novartis, Cephalon, MSD, Transgene, BMS, Roche, GlaxoSmithKline, Bayer. Ad-board: Astra Zeneca, Novartis, Cephalon, MSD, Transgene, Genta, Bayer, Roche, BMS, GSK, Spirig. L. Mitchell: Full-time employee of F. Hoffmann-la-Roche. L. Veronese: Full time employee at F. Hoffmann-la-Roche. All other authors have declared no conflicts of interest.