Clinical and surgical outcomes of neoadjuvant targeted therapy in anaplastic and differentiated thyroid cancer.

Abstract

e18143 Background: The use of targeted therapy in anaplastic thyroid cancer (ATC) and differentiated thyroid cancer (DTC) is limited to the advanced setting. Increasingly the use of targeted kinase inhibitors (TKI) are being considered as neoadjuvant therapy (NAT), though the benefit of the approach is not well understood. We reviewed patients with thyroid cancer who received neoadjuvant targeted therapy and describe their surgical and clinical outcomes. Methods: Patients with locally advanced ATC/DTC who received TKI NAT before definitive surgery between 2018-2024 at MSKCC were assessed for radiographic response (clinical read), surgical outcomes, and survival. A single surgical reviewer assessed NAT impact on surgical feasibility, achieving R0 resection, and reducing surgical morbidity (e.g. preservation of recurrent laryngeal nerve, avoiding tracheal resection). The combined impact was classified into: high, moderate, minor and no impact. Survival was assessed by Kaplan-Meir method. Results: Total cohort N=19. 9 ATC BRAFV600E patients received dabrafenib/trametinib (D/T). Also included were 2 oncocytic carcinomas (lenvatinib), 2 medullary carcinoma (selpercatanib), 6 papillary carcinoma (4 lenvatinib, 1 larotrectinib, 1 selpercatanib). Median time on drug therapy was 5 months prior to surgery. Patients who received D/T for ATC derived the greatest benefit (high 4/9 (44%), moderate 3/9 (33%), minor or none 2/9 (22%)). 7/9 (77%) patients with ATC and R0 resection had an 86% survival rate at 24 months, compared to 0% for 2/9 (22%) patients who had R1 resection. 7/10 (70%) of the non-anaplastic patients had R1 resection. 5/10 (50%) of non-anaplastic patients had a high impact from NAT with 3/10 (30%) showing no impact. Radiographically, 16/19 (84%) patients had a partial response, of which 6 had major response (>50% reduction). 3/19 (16%) had stable disease. Locoregional control in the neck was 17/18 (94%) in evaluable patients. Median overall survival was 39.6 months and disease-free survival was 56% at 2 years in the total cohort. Conclusions: TKIs use in the neoadjuvant setting for locally advanced ATC/DTC is feasible and may alter surgical extent and survival outcomes. Further prospective study of this strategy in ATC/DTC is warranted.