Incorporation of radioactive iodine into RR-TC with inhibition of MAPK (ERRITI)
In resectable radioactive iodine-resistant thyroid cancer, inhibition of mitogen-activated protein kinases (MAPKs) restored iodine incorporation (redifferentiation) (RR-TC). However, in BRAFV600E-mutant (BRAF-MUT) RR-TC results were disappointing. Here, researchers assessed the feasibility and efficacy of redifferentiation therapy in patients with BRAF-MUT or wild-type RR-TC (BRAF-WT) by modulating MAPK based on their genotype. Trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days was administered to patients in this prospective, single-center, phase II, two-arm study 123I-scintigraphy was used to assess redifferentiation. Once radioactive iodine uptake has recovered, 131I therapy guided by 124I was administered. The rate of redifferentiation was the primary measure of success. Response to treatment (thyroglobulin, RECIST 1.1) and safety were secondary objectives. The investigators used an analysis of the operating characteristics of the receiver and the Youden J statistics to assess which parameters most reliably predict effective redifferentiation. Approximately 7 of 20 (35%) patients, including 2 of 6 (33% in the BRAF-MUT group and 5 of 14 (36%) in the BRAF-WT group, experienced redifferentiation. The median (interquartile range) 131The therapeutically active dose administered to patients was 300.0 (273.0-421.6) mCi. Approximately 71% (5/7) of patients showed a decrease in thyroglobulin, 14% (1/14) showed no change, while the remaining patients had stable or progressive disease by RECIST 1.1 criteria. (SUVpeak) less than 10 to 2[18F] A positive fluoro-2-deoxy-D-glucose (FDG)-PET result was linked to redifferentiation (P=0.01). Only 1 patient presented transient pyrexia (grade 3) and 1 presented a rash (grade 4). It was shown that approximately 1/3 of patients in each group experienced effective redifferentiation after receiving genotype-guided MAPK inhibition. Thyroglobulin (Tg) levels fell in more than half of those who received 131I therapy afterwards. The success of redifferentiation can be predicted by a low level of tumor glycolysis, as measured by FDG-PET.