Checkpoint Inhibition in Addition to Dabrafenib/Trametinib for BRAF V600E -Mutated Anaplastic Thyroid Carcinoma

作者：Sarah Hamidi, Priyanka Chandrasekhar Iyer, Ramona Dadu, Maria Kristine Gule-Monroe, Anastasios Maniakas, Mark Zafereo, Jennifer Rui Wang, Naifa Lamki Busaidy, Maria E. Cabanillas · 发表于：Thyroid · 年份：2024 · DOI：10.1089/thy.2023.0573 · 被引用次数：81 · 研究领域：Cancer-related Molecular Pathways、Cancer Mechanisms and Therapy、Melanoma and MAPK Pathways

Background: The dabrafenib plus trametinib combination (DT) has revolutionized the treatment of BRAF V600E -mutated anaplastic thyroid carcinoma (BRAFm-ATC). However, patients eventually develop resistance and progress. Single-agent anti-PD-1 inhibitor spartalizumab has shown a median overall survival (mOS) of 5.9 months. Combination of immunotherapy with BRAF/MEK inhibitors (BRAF/MEKi) seems to improve outcomes compared with BRAF/MEKi alone, although no direct comparison is available. BRAF-targeted therapy before surgery (neoadjuvant approach) has also shown improvement in survival. We studied the efficacy and safety of DT plus pembrolizumab (DTP) compared with current standard-of-care DT alone as an initial treatment, as well as in the neoadjuvant setting. Methods: Retrospective single-center study of patients with BRAFm-ATC treated with first-line BRAF-directed therapy between January 2014 and March 2023. Three groups were evaluated: DT, DTP (pembrolizumab added upfront or at progression), and neoadjuvant (DT before surgery, and pembrolizumab added before or after surgery). The primary endpoint was mOS between DT and DTP. Secondary endpoints included median progression-free survival (mPFS) and response rate with DT versus DTP as initial treatments, and the exploratory endpoint was mOS in the neoadjuvant group. Results: Seventy-one patients were included in the primary analysis: n = 23 in DT and n = 48 in DTP. Baseline demographics were similar between groups, including the...