Abstract Introduction: Radioactive iodine refractory papillary thyroid cancers (PTC) containing BRAF-V600E mutations can be treated with BRAF/MEK inhibitors (BRAF/MEKi), but their effectiveness compared to tyrosine kinase inhibitors (TKI) and immunotherapy (IO) remains unclear. Therefore, we compared real-world survival and molecular/transcriptional signatures in patients with BRAF-mut and BRAF-wildtype (wt) PTC. Methods: Thyroid tumor samples underwent DNA/RNA next-gen sequencing and immunohistochemistry at Caris Life Sciences. Tumor microenvironment (TME) cell fractions were estimated by RNA deconvolution using QuanTIseq. Insurance claims data was used to infer real-world overall survival (OS) and time on treatment. Results: A total of 1348 patients with differentiated thyroid cancer were identified; 81.8% were classified as PTC, of which 68.4% harbored a BRAF-V600E mutation. TERT promoter mutations were the most common mutation in PTC (72%), and more prevalent in BRAF-mut versus (vs) BRAF-wt. Mutations in NRAS, HRAS, and KRAS, as well as RET, BRAF, and ETV6 gene fusions, were predominantly found in BRAF-wt PTC. BRAF-mut PTC were more often PD-L1+ (33% vs. 18%, p0.001) and had significantly higher IFNγ scores. OS was not significantly different between patients with BRAF-mut vs wt PTC. Systemic treatment (BRAF/MEKi, TKI or IO) was not associated with significant differences in OS in BRAF-mut PTC, although there was a trend for longer OS in those treated with TKI compared to BRAF/MEKi or IO. Conclusions: BRAF-mut PTC is associated with a pro-inflammatory TME milieu compared to BRAF-wt PTC. However, in this limited data set, treatment choice was not associated with differences in OS in BRAF-mut PTC.
Chirra et al. (Fri,) studied this question.