Dabrafenib and trametinib in the treatment of BRAF-mutated anaplastic thyroid cancers (ATC).

Abstract

6093 Background: ATCs are rare, aggressive tumors with poor median overall survival (OS). Approximately 45% harbor BRAF V600 mutations driving tumor progression. We evaluated the outcomes of BRAF-V600E-mutated ATC treated with dabrafenib and trametinib (D/T), with or without local therapy. Methods: Consecutive ATC patients with BRAF-V600E mutations treated at our institution from 2016-2024 that received D (150 mg twice daily) and T (2 mg once daily) as a component of their multiple lines of therapies were included. Locoregional therapies included surgery alone, surgery and radiation, or radiation alone. We reported the OS of these patients. Results: Out of 82 BRAFV600E mutated ATC patients, 61 pts. (74%) were metastatic at the time of D/T initiation. Median age was 71 years (range 47-86 yrs). Locoregional therapies given: surgery only (n=8); surgery and RT (n=24); RT only (n=23). Median follow-up for all patients is 10 months, and 19 months for alive patients. Median OS for all patients is 14 months. Among those who had surgery only (n=8), the median OS was not reached. Patients who had surgery and radiation had a median OS of 22 months. Lastly, the patients who had RT only as local therapy had a median OS of 14 months. Patients without residual ATC after surgery had a median OS of 39 months versus 21 months for those with residual neck disease. 14 patients who received D/T prior to surgery had a median OS of 39 mo. Table 1 provides details of outcomes by metastatic status. Conclusions: This is the largest study to date reporting on outcomes of patients with BRAF V600 mutated ATC receiving D/T. This regimen demonstrates highly favorable results. Our data suggests that patients should undergo surgery when feasible and that D/T should be given prior to surgical intervention. However, the optimal timing, integration as well as the types of local therapy should be prospectively evaluated. Patient outcome by metastatic status. Overall Survival M0 (N=21) M1 (N=61) All Patients Median Follow-up (all) 15 months (range 2-49) 9 mo (range 0-71) Median Follow-up (alive) 34 mo. (range 7-49) 16 mo. (range 0-71mo) Median OS 22 mo. (95% CI 4-40mo.) 10 mo. (95% CI 5-15mo.) 12-month 66% 48% 18-month 55% 37% Surgery (vs. No surgery) N=13 versus N=8 N=19 versus N=42 Median OS 22 mo. versus 10 mo. 28 mo. versus 9 mo. 12-month 77% versus 47% 68% versus 38% 18-month 68% versus 47% 61% versus 25% Surgery* (No residual neck disease versus residual) N=5 versus N=8 N=15 versus N=4 Median OS Not reached versus 22 mo. 39 mo. versus 9 mo. 12-month 80% versus 75% 73% versus 50% 18-month 53% versus 47% 65% versus 50% Radiation (vs. No RT) N=6 versus N=2 N=17 versus N=25 Median OS 7 mo. versus 10 mo. 9 mo. versus 6 mo. 12-month 50% versus 0% 41% versus 36% 18-month 50% versus 0% 29% versus 22% Surgery + RT N=6 N=12 Median OS 22 mo. 21 mo. 12-month 75% 58% 18-month 55% 58% Order of D/T Before Surgery N=3 N=11 Median OS Not reached 28 mo. 12-month 100% 82% 18-month 67% 72% *Surgery with or without RT.