Updated efficacy and safety data of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated anaplastic thyroid cancer (ATC)

Abstract

Background: Patients (pts) with differentiated thyroid cancer (DTC) are a heterogeneous group. Tumor growth rate (TGR) is correlated with life expectancy. Lenvatinib (LEN) is approved for radioiodine‐refractory DTC based on the phase 3 SELECT trial. Here we examine TGR and efficacy outcomes from SELECT. Methods: Per SELECT eligibility criteria, pts had independent radiologic evidence of progression within 13 months prior to randomization (prebaseline) to LEN or placebo (PBO). In this post hoc, exploratory analysis, pre‐randomization TGR was assessed per pt as: (sum of target lesions at baseline ‐ sum of target lesions at prebaseline) divided by sum of target lesions at prebaseline, and then divided by the interval of time between the 2 examinations (in mos). Pts were dichotomized: slow TGR (TGR ≤ median TGR of all SELECT pts) vs fast TGR (TGR > median). Subgroups were: baseline liver metastases (yes vs no), age (≤65 vs>65 y), histology (papillary vs follicular), ECOG PS (0 vs≥1), and baseline thyroid‐stimulating hormone (TSH) (≤0.1 vs>0.1 uIU/mL). Results: In a multivariate model, TGR of pts on LEN was significantly associated with baseline tumor size, and baseline liver, bone, and other metastases. When comparing treatment arms, LEN improved progression‐free survival (PFS) vs PBO in both slow TGR (median 20.2 vs 3.7 mos; HR 0.19; 95% CI 0.12‐0.32; P<0.001) and fast TGR groups (median 14.8 vs 3.5 mos; HR 0.20; 95% CI 0.12‐0.33; P<0.001). PFS of LENtreated pts was significantly longer in the slow vs fast TGR group (median 20.2 vs 14.8 mos; HR 0.62; 95% CI 0.41‐0.94; P=0.0232). Differences were also seen for PFS between slow and fast TGR groups in pts >65 years, pts with ECOG PS 0, and pts with baseline TSH>0.1 uIU/mL. When comparing treatment arms, overall survival (OS) trends favored LEN over PBO in both slow (medians not reached [NR]; HR 0.53; 95% CI 0.29‐0.97) and fast TGR groups (LEN, NR vs PBO, 20.3 mos; HR 0.78; 95% CI 0.43‐ 1.39); however, significance was not achieved in the fast TGR group. Among pts on LEN, OS was similar between slow and fast TGR groups (HR 0.77; 95% CI 0.46‐1.29); no trends were seen in subgroup analyses. Conclusions: In SELECT, LEN conferred benefit over PBO for all pts regardless of TGR; however, PFS was significantly longer in pts with slower TGR.