Valuable insights from real-life experiences of advanced thyroid cancer treatment with sorafenib in Latin America
Archives of Endocrinology and Metabolism
A pproximately 10,000 new cases of thyroid cancer are diagnosed annually in Brazil (1), most of the cases are associated with a survival rate of over 98% 5 years after diagnosis, but 10-20% present or eventually develop distant metastases (2,3). Until recently, the only effective treatment for distant metastatic disease was radioactive iodine (RAI) and the prognosis of patients who failed RAI therapy was poor, the 10-yr survival rate being only 10% (4). From these, patients with enlarging and
... G-PET positive lesions are the ones with the lowest rates of survival (5). With the knowledge that oncogenic kinases play a significant role in tumorigenesis and disease progression several kinase inhibitors have been investigated and became approved therapies. Based on phase III, placebo-controlled trials, multi-kinase inhibitors such as sorafenib (DECISION) and Lenvatinib (SELECT) have been approved by the Federal and Drug Administration (FDA) in 2013 and 2015 and by ANVISA in 2015 and 2016, respectively. In the DECISION trial (N=417), patients on sorafenib had significantly longer progression-free survival (PFS) compared to placebo (10.8 months versus 5.8 months (HR: 0.59; IC 95%: 0.45 -0.76; p < 0.0001) as well as a higher response rate (RR) (12.2% versus 0.5%) with no difference in overall survival (OS). The most common adverse events, observed in more than 50% of patients, included hand and foot skin syndrome (HFS), diarrhea, alopecia, and rash. Hypertension was observed in 40.6% of patients (6). In the SELECT trial (N=392), the median PFS was 18.3 months in those who received lenvatinib compared to 3.6 months in the placebo group (HR 0.21; IC 99%: 0,14 -0.31; p < 0.001) and the RR was 64.8% versus 1.5% in the placebo arm. Taking into consideration the entire cohort there was no significant improvement in overall survival, but subgroup analysis identified improved OS in older patients (> 65 years) and in patients with lung metastases (> 1 cm) (7-9). Adverse events were frequent, 97.3% of patients experienced some form of an adverse event. Most frequently, patients experienced hypertension (67.8%), diarrhea (59.4%), fatigue (59%), weight loss among others (7). New therapies for radioactive iodine refractory advanced thyroid cancer continue to emerge. Precision medicine has become a reality, mainly in private medicine, and the treatment is switching from promiscuous multi-targeted kinase inhibitors to the specific inhibition of the mutated pathway found in tumor genotyping.