A pilot study of trametinib in combination with paclitaxel in the treatment of anaplastic thyroid cancer.

Abstract

6088 Background: Anaplastic Thyroid Cancer (ATC) is a rare and highly aggressive tumor with extremely poor prognosis. Outside of the recent approval of dabrafenib/trametinib for BRAF mutant tumors, there are no other standard treatment available for metastatic ATC. The majority of ATC is driven through the MAPK pathway. Data in lung cancer suggested synergy with trametinib, a MEK inhibitor, and taxanes. Methods: In this pilot study we used Trametinib (2 mg) daily with Paclitaxel (80 mg/m2) administered weekly for the first 3 weeks out the 4 week-cycle. Restaging imaging was performed every 6-8 weeks (1.5-2 cycles). Eligible patients had ATC with baseline ECOG performance status ≤ 1 and were enrolled at Memorial Sloan Kettering Cancer Center. Prior treatment allowed. Prior brain metastases were allowed if treated and stable off of steroids. Primary objective was PFS at 6 months with the target of > 2 subjects out of 12 at the time point. Results: 12 patients (6 men and 6 women) were enrolled between 11/2017 and 10/2021. Seven (58%) had prior radiation to the neck; 4 (33%) had prior treatment (not including with radiation) for ATC; 1 (8%) had prior brain metastases. Three (25%) partial responses were reported, and five (41.67%) reported stable disease. Subjects with partial responses had a BRAF V600E mutation (1), BRAF fusion gene (1), and a RAS mutation (1). Median time on treatment was 10.5 weeks (3-47+ weeks). Median overall survival was 26 weeks (3-59+). Six-month progression free survival (PFS) was achieved in 3 patient (25%), one of whom remains on study. 2 patients discontinued treatment due to unacceptable toxicity. The most frequent adverse events observed (all grades) were anemia (75%), increased AST, diarrhea and leukopenia (all 50%). Grade 3/4 AEs included neutropenia (25%), with anemia, AST increased, febrile neutropenia, and lymphopenia, all 16.67%. Grade 4 reactions included lymphopenia (n = 2) and leukopenia (n = 1). Conclusions: Our target progression-free survival (PFS) at 6 months was observed on this study. The combination of trametinib and paclitaxel should be evaluated in a larger cohort of patients in the future. Clinical trial information: NCT03085056.