Modern Therapeutic Strategies in Anaplastic Thyroid Carcinoma: Real-World Outcomes of Targeted Therapy and Immunotherapy

Background: Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive malignancy associated with a dismal prognosis. Although the introduction of molecularly targeted therapies and immune checkpoint inhibitors has expanded systemic treatment options, real-world outcomes remain variable. Moreover, rapid clinical deterioration frequently limits access to systemic therapy, potentially constraining therapeutic benefit. Materials and Methods: We conducted a retrospective cohort study of patients with ATC managed at the Royal Marsden Cancer Centre between 2015 and 2024. Demographic, molecular, and treatment-related data were collected. Tumour response was assessed according to RECIST version 1.1. Time to response (TTR) was compared between treatment strategies using the Mann–Whitney U test. Duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan–Meier method, with exploratory Cox regression analyses performed to evaluate potential predictors of outcome. Systemic treatment exposure analyses focused on dabrafenib plus trametinib and immunotherapy in any line of therapy. Results: Forty-four patients were included. Thirty patients (68%) received at least one line of systemic therapy, while 14 patients (32%) did not receive systemic treatment, primarily due to rapid clinical deterioration. Among untreated patients, median OS from diagnosis was 3.3 months, with a high rate of early mortality. Among treated patients, the median time from diagnosis to initiation of systemic therapy was 2.6 months, a duration comparable to the survival observed in untreated patients, highlighting a narrow therapeutic window. Two cohorts of treated patients were identified: patients exposed in any line to dabrafenib plus trametinib (n = 16) and patients exposed in any line to immunotherapy (n = 16). As some patients received sequential systemic therapies, cohorts were not mutually exclusive. Among patients with BRAF-mutated ATC treated with dabrafenib plus trametinib in any line, the objective response rate (ORR) was 68.8%, including two complete responses. Median PFS was 6.3 months (95% CI, 1.8–37.4), median OS was 15.1 months (95% CI, 2.8–NR), and the estimated 2-year OS rate was 31.8%. Among patients treated with immunotherapy in any line, ORR was 40.0%, including one complete response. Median PFS was 4.2 months (95% CI, 1.8–NR), median OS was 7.4 months (95% CI, 3.8–NR), and the estimated 2-year OS rate was 42.9%. Median time to response (TTR) showed a non-significant trend favouring dabrafenib plus trametinib over immunotherapy (2.2 vs 5.8 months; p = 0.11). Median duration of response (DoR) was 4.2 months with dabrafenib plus trametinib and 2.1 months with immunotherapy, although formal comparisons were limited by censoring and the retrospective study design. Conclusions: In real-world practice, outcomes of modern systemic therapies in ATC are strongly shaped by access to treatment and feasibility of delivery. D+T provides rapid and clinically meaningful responses in BRAF-mutated ATC, whereas immunotherapy can confer durable benefit in a subset of patients. Nonetheless, aggressive disease biology and early clinical deterioration frequently limit therapeutic impact, underscoring the importance of streamlined diagnostic pathways, faster treatment initiation, and improved patient selection strategies.