Dr. Kunadharaju and Dr. Goyal are house officers in the Department of Internal Medicine, and Dr. Silberstein is a professor and chief of hematology/oncology, all at CHI Creighton University Medical Center in Omaha,Nebraska. Dr. Rudraraju is a house officer at MacNeal Hospital in Berwyn, Illinois. Dr. Silberstein is also chief of oncology at the VA Nebraska-Western Iowa Healthcare System in Omaha.
References
patients with BRAF and RAS mutations and wild-type BRAF and RAS subgroups had a significant increase in median PFS in the sorafenib treatment group compared with the placebo group (Table 1). 20
Adverse events (AEs) occurred in 98.6% of patients receiving sorafenib during the double-blind period and in 87.6% of patients receiving placebo. Most AEs were grade 1 or 2. The most common AEs were hand-foot-skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%). Toxicities led to dose modification in 78% of patients and permanent discontinuation of therapy in 19%. 20 Like other BRAF inhibitors, sorafenib has been associated with an increased incidence of cutaneous squamous cell carcinomas (5%), keratoacanthomas, and other premalignant actinic lesions. 21
Lenvatinib
In February 2015, lenvatinib was approved for the treatment of locally recurrent or metastatic, progressive DTC that no longer responds to radioactive iodine treatment. 22 Lenvatinib is a MKI of VEGFRs 1, 2, and 3; fibroblast growth factor receptors 1 through 4; PDGFR-α; RET, and KIT. 23,24 The recommended dose is 24 mg orally once daily.
Schlumberger and colleagues published results from the SELECT trial, a randomized, double-blinded, multicenter phase 3 study involving 392 patients with progressive thyroid cancer that was refractory to iodine-131. 25 A total of 261 patients received lenvatinib, and 131 patients received a placebo. Upon disease progression, patients in the placebo group were allowed to receive open-label lenvatinib. The study’s primary endpoint was PFS. Secondary endpoints were the response rate (RR), OS, and safety. The median PFS was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (HR, 0.21; 99% CI, 0.14-0.31; P < .001). The RR was 64.8% in the lenvatinib group (4 complete and 165 partial responses) and 1.5% in the placebo group (P < .001). There was no significant difference in OS between the 2 groups (HR for death, 0.73; 95% CI, 0.50-1.07; P = .10). This difference became larger when a potential crossover bias was considered (rank-preserving structural failure time model; HR, 0.62; 95% CI, 0.40-1.00; P = .05). 25
In a subgroup analysis, median PFS was about 14 months in the absence of prior anti-VEGFR therapy and 11 months of prior therapy. The treatmentrelated AEs were 97.3% in the lenvatinib group, and 75.9% were grade 3 or higher. Common treatmentrelated AEs of any grade in the lenvatinib group included hypertension (67.8%), diarrhea (59.4%), fatigue or asthenia (59.0%), decreased appetite (50.2%), decreased weight (46.4%), and nausea (41.0%). The study drug had to be discontinued because of AEs in 14% of patients who received lenvatinib and 2% of patients who received placebo. In the lenvatinib group, 2.3% patients had treatment-related fatal events (6 patients). 25
Summary
Patients with DTC who progress after radioactive iodine therapy, TSH suppressive therapy, and external beam radiotherapy should be considered for systemic therapy. Systemic therapy consists
