Impact of targeted therapies (TT) and immunotherapy (IO) on outcomes in patients (pts) with anaplastic thyroid carcinoma (ATC): International data from the Spanish GETNE registry.

e18154 Background: The systemic treatment landscape in ATC is rapidly evolving, with promising therapies such as BRAF-targeted therapy (TT) and immunotherapy (IO). Despite the historically poor prognosis of ATC, certain patient populations achieve prolonged progression-free survival (PFS) with these treatments. While conventional chemotherapy (CT) has limited efficacy, it remains a key component of the treatment sequencing. This study aim is to describe treatment outcomes in a nationwide cohort of ATC patients (pts) in the era of novel systemic therapies. Methods: A retrospective analysis of ATC pts was conducted using the Spanish Registry of Advanced Thyroid Cancer (REGETNE-TIROIDES) across 17 centers in Spain and Portugal. Baseline demographic and clinical characteristics, molecular profiling, types of systemic treatment, treatment outcomes, and overall survival (OS) were analyzed. Results: A total of 214 pts (age 70y, 56.5% female) were included. 8.4% had stage IVA, 34.5% IVB, and 57.1% IVC at diagnosis. Next-generation sequencing (NGS) was performed in 81.8% of pts, identifying frequent alterations, including BRAF (25%), P53 (15.5%), NRAS (14.2%), TERT (12.2%), and PAX8 (10.1%). One ALK-rearrangement and no RET or NTRK were identified. First-line systemic therapy was given to 67.2% of pts: CT (32%), TT (10.4%), and MKI-IO combinations (7.2%). Second-line therapy was given to 46.7%, mostly chemotherapy. Among BRAF-mutant population, TT was used as first-line treatment in 46.2%. The median OS of the cohort was 4.5 months. Multivariate analysis identified NGS access and BRAF mutation as significant prognostic factors. Metastatic pts treated with IO (17.5 vs 2.8 months, p=0.002) or MKI-IO combo (21 vs 4.3 months, p=0.007) had significantly improved survival. However, TT in the BRAF-mutant population showed not significantly impact on OS (10.1 vs 5.7 months). Conclusions: Access to NGS and the use of IO or IO combinations are key factors associated with improved OS in ATC pts. Further clinical trials are needed to explore additional treatment strategies for this challenging population.