Abstract 2719: Accelerated BRAF mutation analysis using a fully automated PCR platform improves the management of patients with metastatic melanoma : MELFAST trial

Abstract

Abstract Background : Molecular diagnosis has become a standard of care in many cancers and BRAF mutations analysis in FFPE tumor specimens is needed to initiate personalized therapy using BRAF tyrosine kinase inhibitor (vemurafenib, dabrafenib) in BRAF-mutated metastatic melanoma. Accelerated BRAF mutation analysis is achievable using CE-IVD fully automated (FA) PCR-based platform (Idylla, Biocartis) and enables the determination of BRAF mutational status in less than 2 hours including sample preparation and proved suitable for routine molecular diagnosis of metastatic melanoma (Harlé et al. PloS ONE 11(4); e0153576). Patients and methods : MELFAST trial is an observational monocentric study aiming at evaluating the clinical impact of reducing BRAF status determination delay in patients with metastatic melanoma. 40 patients (pts) were included in MELFAST trial, 31 pts were included retrospectively with BRAF mutation analysis being performed according to standard operating procedures (SOP) using conventional PCR, 10 pts were included prospectively with BRAF mutation analysis being performed using FA-PCR. Results : Among the 40 pts included, 3 pts were excluded because of violation of inclusion criteria. 37 pts that were analyzed (29 pts with retrospective inclusion and 8 pts with prospective inclusion). BRAF mutational status was not known at the time of treatment decision in 11/29 (38%) pts included retrospectively and in all the pts included prospectively. Using FA-PCR enables to provide BRAF mutational status within the same day for most of the samples and the reporting delay was significantly reduced using FA-PCR as compared to SOP (0 vs 7 days, p<0.001) and the delay of initiation of anti-BRAF therapy was subsequently reduced (16 vs 26 days, p=0.035). This reduced delay was found to be consistent with that observed when BRAF mutational status had been anticipated and was already available at the time of treatment line decision (20 days, p=0.798). Conclusion: As compared to conventional SOP, using FA-PCR accelerates BRAF mutation analysis reporting and significantly reduces the delay before initiation of personalized therapy in pts with metastatic melanoma. This warrants the investigation of the impact on the patients outcome i.e. progression free and overall survival. Citation Format: Alexandre Harlé, Delphine Serre, Julia Salleron, Marie Husson, Agnès Leroux, Lionnel Geoffrois, Jean-Louis Merlin. Accelerated BRAF mutation analysis using a fully automated PCR platform improves the management of patients with metastatic melanoma : MELFAST trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2719. doi:10.1158/1538-7445.AM2017-2719