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Program Number: AHNS26
Session Name: Scientific Session 6 - Endocrine
Session Date: Thursday, May 15, 2025
Session Time: 1:00 PM - 1:45 PM

Neoadjuvant BRAF/MEK inhibitor therapy and immunotherapy for BRAFV600E-mutated anaplastic thyroid cancers

Isabelle Fournier, MD, FRCSC; Anastasios Maniakas, MD, PhD, FRCSC; Jennifer Rui Wang, MD, PhD, ScM, FRCSC; Victoria E. Banuchi, MD, MPH; Stephen Y. Lai, MD, PhD, FACS; Maria Gule-Monroe, MD; Shekhar D. Khanpara, MD; Matthew S. Ning, MD, MPH; Michelle D. Williams, MD; Xu Li, PhD; Ramona Dadu, MD; Naifa L. Busaidy, MD, FACP, FACE; Priyanka Iyer, MBBS; Sarah Hamidi, MD, FRCPC; Maria E. Cabanillas, MD; Mark E. Zafereo, MD, FACS; MD Anderson Cancer Center

Importance: BRAF/MEK inhibitors and immunotherapy are novel treatment options for patients with BRAFV600E mutated anaplastic thyroid carcinoma (BRAFm-ATC).

Objective: The primary objective was to determine overall survival (OS), progression-free survival (PFS) and Response Evaluation Criteria in Solid Tumors (RECIST) for BRAFm-ATC patients treated with BRAF/MEK inhibitors +/- immunotherapy.

Design, settings, and participants: From 2017 to 2024, 153 patients with BRAFm-ATC who received at least 4 weeks of BRAF/MEK inhibitor therapy, +/- immunotherapy, were retrospectively reviewed. BRAFV600E mutation was positive either by immunohistochemistry (IHC) alone (16%), tumor next generation sequencing (NGS) alone (10%), blood NGS (liquid biopsy) alone (3%) or a combination of methods (71%). BRAF/MEK inhibitors used included dabrafenib/trametinib (89%) and vemurafenib/cobimetinib (11%). Additionally, 135 patients (88%) received immunotherapy.

Main outcomes and measures: OS, PFS, and RECIST version 1.1 tumor response were assessed. Baseline CT imaging prior to BRAF/MEK inhibitor therapy and the best response CT imaging were used to evaluate tumor response.

Results: Patients were classified as stage IVb (31%) or stage IVc (69%). Amongst all 153 patients, 44 (29%) had upfront surgery before receiving BRAF/MEK inhibitors (1-year OS of 87.2% [confidence internal (CI) 76.6-97.7] and 3-year OS of 66 % [CI 48.6-83.4]), while 109 (71%) had neoadjuvant BRAF/MEK inhibitor +/- immunotherapy. Following neoadjuvant therapy (n = 109), RECIST complete response (CR) was observed in 6 patients (6 %), partial response (PR) in 72 patients (66%), stable disease (SD) in 20 patients (18%), progressive disease in 2 patients (2%) and was not evaluable in 9 patients (8%).

Ultimately 72/109 (66%) patients had surgery after median 3 months [1-24] of neoadjuvant therapy, with 1-year OS of 91.2% [CI 84.4-97.9] and 3-year OS of 65.7% [CI 53.1-78.3]. For 37 (34%) patients who did not have surgery after neoadjuvant therapy, 1-year and 3-year OS were 51.4% [CI 34.9.9-68] and 20.4% [CI 14.6-30.7], respectively.  

In the neoadjuvant followed by surgery group (n=72), 35 patients (49%) had pathologic ATC complete response (either papillary thyroid cancer (PTC) alone, n= 31; or no tumor in the specimen, n=4), while another 37 patients (51%) had residual ATC in the surgical specimen after neoadjuvant therapy (either ATC alone, n = 21; or ATC+PTC, n =16). ATC complete response group had a 3-year OS of 92.8 % [CI 83.3-100] while ATC residual group had a 43.2% [CI 25.3-61.2] 3-year OS (p=0.001).

Conclusions and relevance: Most patients with BRAFm-ATC had complete or partial RECIST response after BRAF/MEK inhibitor +/- immunotherapy, such that approximately 2/3rd’s were able to ultimately undergo surgery.  

Keywords: Anaplastic thyroid cancer, BRAFV600E mutation, BRAF/MEK inhibitors, immunotherapy, neoadjuvant, surgery, survival, RECIST 

 

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