BRAF V600 Metastatic Melanoma Research Articles

Vemurafenib (V) in BRAF V600E metastatic melanoma (mM): Analysis of 507 patients (pts) enrolled in the French temporary authorization for use (ATU).

8591 Background: V, a selective BRAF inhibitor, significantly improves OS in BRAF mutated mM. ATU is an exceptional measure making available drugs that have not yet been granted a Marketing Authorisation. We provide demographic data of pts treated by V in the ATU. Methods: V 960 mg BID was given to pts with unresectable stage IIIC or IV BRAF V600E mM. Genotyping was done on the national network of molecular genetics platforms funded by the Institut National du Cancer. Data were prospectively collected. Results: From Apr 2011 to Jan 2012, 83 sites enrolled 507 pts. 80% were treated by oncodermatologists. Pts characteristics at baseline are summarized below. Safety and efficacy data are being evaluated. Conclusions: Around 2 out of 3 patients with a BRAF mutated mM were enrolled in France in the ATU highlighting a large access to BRAF genotyping and to V. Demographic data differs from literature and clinical trials for: site of primary melanoma (reverse trunk/extremity ratio) and inclusion of pts with brain metastasis or PS>2 (excluded in CT). A high number of pts had risk factors for NMSC emphasizing the importance of the communication between oncologists and dermatologists for managing V therapy. [Table: see text]

Predicting early relapse in patients with BRAFV600E melanoma with a highly sensitive blood BRAF assay.

8516 Background: Many patients (pts) with metastatic melanoma (MM) who progress on BRAF inhibitors (BRAFi) develop rapidly progressive disease (PD) which is difficult to manage. Identification of an early marker of PD may allow for therapeutic intervention prior to clinical deterioration. We have developed a highly sensitive and inexpensive assay in our laboratory which can detect as little as 1 BRAFV600E mutant melanoma cell in 400,000 peripheral blood lymphocytes (PBL). We aimed to determine the utility of our assay as a tool to follow pts with BRAF mutant MM who are being treated with a BRAFi. Methods: Every pt had a BRAFV600E mutation detected from a tumor sample in a CLIA-approved laboratory prior to commencing BRAFi therapy. 20 pts with stage IV BRAFV600E MM underwent serial venopunctures before and every 4 weeks during treatment with a BRAFi. BRAFV600E level was quantified using our proprietary assay (Panka et al Melanoma Research 2010). Serial BRAFV600E levels were generated for every pt and normalized to the pre-treatment value. BRAFV600E level was then correlated with response to therapy and PD. Results: BRAFV600E was detected in the PBL of each pt. To date, 10 pts have had BRAFV600E levels quantified at 3 or more time points (data for all 20 pts will be available at time of presentation). Relative BRAFV600E levels reduced by half following the first and second cycles of treatment in 7 pts, which correlated with disease regression in each pt. Following the third cycle of treatment, the relative BRAFV600E levels varied greatly with a subset of pts having continued suppression while others having a rise in their BRAFV600E levels. In each pt with PD, the BRAF assay showed an increase > 4 wks in advance of clinically or radiographically defined PD. Conclusions: Our assay is able to quantify changes in BRAFV600E levels in the blood of pts with BRAF mutant MM receiving BRAFi therapy. In these pts, the BRAFV600E levels are reduced in the setting of initial disease regression and increase well in advance of clinical or radiographic PD. While further development is necessary, such a test could be used to identify pts who may be selected to receive alternative therapy prior to clinical or radiographic PD.