BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

Abstract

The U.S. Food and Drug Administration–approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine–refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30–40%. In this review, we discuss BRAF inhibitors in the context of thyroid cancer, the toxicities associated with BRAF inhibitors, and the suggested management of those toxicities. The management of vemurafenib and dabrafenib toxicities is applicable across all tumor types and may serve as a practical guide to their use.

Novel Therapies Against Aggressive Differentiated Thyroid Carcinomas

“…Severe AEs were noted in 65 and 68% of the two groups, respectively, [29,48] with 22% developing cutaneous squamous cell carcinoma [28,30].…”

“…Vemurafenib and dabrafenib are small inhibitors highly selective to the BRAF-V600E mutations, which are being studied in Phase II trials [27][28][29][30].…”

“…Vemurafenib was efficient in some BRAFV600E-positive advanced RAIRTC patients (partial responses of 35-38.5% in naive patients and 26-29% in those previously exposed to a VEGFR inhibitor) [29][30][48][49]. Severe AEs were noted in 65 and 68% of the two groups, respectively, [29,48] with 22% developing cutaneous squamous cell carcinoma [28,30].…”

“…Dabrafenib associated with trametinib revealed promising results in recurrent TC [27,28]. The most common AEs with these drugs are dermatological, gastrointestinal and constitutional [28,30].…”

Relevance of BRAF and NRAS mutations in the primary tumor and metastases of papillary thyroid carcinomas

“…BRAF T1799A mutation was also found to be diagnostically useful in the preoperative detection of PTC in fine‐needle aspiration biopsies (FNABs) by unmasking cytopathology false‐negative results . BRAF T1799A mutation also recently emerged as a promising therapeutic target, and several selective and nonselective inhibitors are being tested in melanoma, thyroid, and colon cancers with encouraging results …”