1134P BRAF codon 600 mutations in patients diagnosed with melanoma in the UK; An audit to assess variation in mutation frequency & methods between clinical testing centres

Abstract

Background: The published frequency of the BRAF p.V600 mutations in patients with melanoma is approximately 40% and is dependent on age and melanoma subtype. BRAF status is a key predictive factor for response to targeted therapy and immunotherapy and there is increasing evidence that it is also prognostic. Mutation testing is a standard of care for patients with resected Stage 3 and for Stage 4 disease, to inform treatment choice. There are currently a variety of validated and approved methods for BRAF testing. The primary aim of this study was to identify all clinical laboratories in the UK performing BRAF testing for melanoma and examine the assays used, positivity rates and turnaround time. Methods: This was a retrospective audit of laboratories performing BRAF gene mutational analysis in melanoma samples in the UK. 14 out of the 18 identified laboratories participated. Methodologies used and anonymised results for samples tested Jan-Dec 2019 were collected. Results: 4050 results were analysed. The median BRAF positivity rate amongst all laboratories was 34% (range 23-41%). The median turnaround time for reporting results was 7 calendar days. 6 laboratories used only one method of testing and 8 laboratories used more than one. The types of tests used varied between the testing centres. All laboratories are able to detect clinically important BRAF p.V600E and p.V600K mutations. Men (p= 0.0354) and younger patients (p <0.001) had higher rates of BRAF mutation. the range of median age per laboratory was 65-72. Conclusions: The median reported BRAF positivity rates in the UK is lower than published and there is a wide range. The reasons for the difference in the positivity rates are likely multiple but could potentially have an impact on treatment options offered to patients. Further research is required to identify the reasons for these differences. This will include collaboration with the UK National External Quality Assessment Scheme to optimise the methodologies used across centres, aiming for more consistent results across the board. Legal entity responsible for the study: The Christie NHS Foundation Trust. Funding: Has not received any funding. Disclosure: M. Charakidis: Honoraria (self), To attend virtual ASCO: Novartis. F.H. Blackhall: Honoraria (self): Roche. P. Lorigan: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD. All other authors have declared no conflicts of interest.