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Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer with a median survival of 4 months. Recent advances in molecular profiling have shown that up to half of ATCs harbour the BRAF-V600E mutation. The aim of this study was to provide real-world data and experience on the use of combination therapy dabrafenib and trametinib in patients with BRAF-V600E-mutated advanced ATC. We retrospectively evaluated patients with confirmed BRAF-V600E-mutated ATC, defined as patients with locally advanced or metastatic ATC with no locoregional, radical treatment options. Outcomes measured were overall survival, progression-free survival, response rate, discontinuation rate, dose reduction rate and toxicity data. Seventeen patients were evaluated and the mean age was 68 years. Ten patients died by the time of censoring. The median duration of follow-up was 12 months (3–43 months). The estimated median overall survival was 6.9 months (95% confidence interval 2.46 months – upper confidence interval not reached) and the median progression-free survival was 4.7 months (95% confidence interval 1.4–7.8 months). Dose interruptions and/or reductions were common, but none of the patients had to permanently discontinue treatment because of toxicities. Severe toxicities (grades 3 and 4) were uncommon. This study supports the indication of dabrafenib and trametinib in BRAF-V600E-mutated ATC as an effective and well-tolerated treatment in an historically difficult to treat cancer. • Dabrafenib and trametinib increase survival of BRAF-mutant anaplastic thyroid cancer. • Real-world data plug gaps in evidence in rare disease group. • Largest cohort of real-world patient outcomes reported in the literature. • Dabrafenib and trametinib combination is well-tolerated. [ABSTRACT FROM AUTHOR]

BRAF‐mutant melanoma patients can theoretically access both immunotherapy and BRAF‐targeted therapy as treatment for metastatic disease. BRAF‐targeted therapy is increasingly used 1st line for poorer prognostic patients, so we wanted to assess realistic expectations of these patients accessing 2nd‐line immunotherapy. We conducted a retrospective review of clinical outcomes in 25 patients treated over the last 3 years with 1st‐line BRAF‐targeted therapy in a real‐world clinical setting at a UK‐based tertiary centre. Compared with the registration trials, our patients receiving 1st‐line BRAF‐targeted therapy had poorer performance status, higher disease burden, shorter median progression‐free survival (5.05 months, 95% CI: 3.96–8.88) and shorter median overall survival (11.5 months, 95% CI: 6.24 – not reached). Overall response rate was similar, at 64%. On disease progression, median survival was 2.34 months (95% CI: 1.62 – not reached). Only five patients went on to receive 2nd‐line immunotherapy. Metastatic melanoma patients treated with 1st‐line BRAF‐targeted therapy now have different demographics compared with those recruited to registration trials conducted over the last 10 years. In a modern‐day, real‐world setting, these patients should be counselled that only 1 in 5 are likely to receive 2nd‐line immunotherapy and their survival times are expected to be short. [ABSTRACT FROM AUTHOR]