Matthew Garrett, PharmD Candidate 2015 Mercer University College of Pharmacy
The American Cancer Society estimates that there will be 62,450 new cases of thyroid cancer in the year 2015.1 More than 90% of thyroid cancer diagnosis are classified as differentiated thyroid cancer, which is highly treatable with surgery and radioactive iodine.2 About 10%-20% of patients will have a reoccurrence of thyroid cancer. Surgery and radioactive iodine are used to treat the reoccurring cancer, but sometimes the cancer is nonresectable and nonresponsive to radioactive iodine. Lenvatinib is a new drug in phase 3 trials with an indication for the treatment of differentiated thyroid cancer. Lenvatinib is a multi-targeted kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptor (FGFR), and platelet derived growth factor receptors (PDGFR).3
|Title: Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer4|
|Design||Phase 3, randomized, double-blind, multicenter study|
|Objective||To study the efficacy of lenvatinib radioiodine-refractory thyroid cancer|
|Study groups||Lenvatinib group and placebo group|
|Methods||This study had 392 patients from 21 countries were randomly in a 2:1 ratio assigned to receive 24 mg once daily lenvatinib (261 patients) or placebo (131 patients). The authors designed this study to have 90% power to detect a 75% improvement in progression-free survival with lenvatinib versus the placebo group. Throughout the study, safety assessments were performed and included recording of symptoms and vital signs. The authors also performed safety assessments with electrocardiography, echocardiography (including LEVF), hematologic and biochemical laboratory testing, and urinalysis. Tumor assessments were done every 8 weeks in the randomization phase and every 12 weeks in the extension phase.|
|Duration||5 months||Primary Outcome Measure||The primary end point was progression-free survival, which was defined as the time from randomization to the first documentation of disease progression by independent radiologic review or to death, in the intention-to-treat population.|
|Baseline Characteristics||Median age: 64 (lenvatinib) and 61 (placebo)
Bone mets: 104 (lenvatinib) and 48 (placebo)
Pulm mets: 226 (lenvatinib) and 124 (placebo)
|Results||From the 392 patients, 202 patients had disease progression (93 [35.6%] in and 109 [83.2%] in the placebo group), and 18 patients had died before disease progression (14 in the lenvatinib group and 4 in the placebo group). The median progression free survival was 18.3 months (95% CI, 15.1 to not estimable) with lenvatinib as compared with 3.6 months (95% CI, 2.2 to 3.7) with placebo (hazard ratio for progression or death, 0.21; 99% CI, 0.14 to 0.31; P<0.001)|
|Adverse Events||Common Adverse Events: hypertension 67.8%, diarrhea 59.4%, fatigue 59%, weight loss 46.4%, nausea 41%|
|Serious Adverse Events: pulmonary embolism 2.7%, renal failure 4.2%, gastrointestinal fistula 1.5%|
|Percentage that Discontinued due to Adverse Evens: lenvatinib 14.2% and placebo 2.3%|
|Study Author Conclusions||This study showed that lenvatinib, as compared with placebo, was associated with significant prolongation of progression-free survival and an improved response rate (64.8% vs. 1.5%) among patients with iodine-131–refractory
differentiated thyroid cancer. Toxic effects of therapy were considerable, and most toxic effects were managed with dose modification and medical therapy.
This study was able to show that lenvatinib can prolong progression-free survival in patients with non-responsive thyroid cancer. Lenvatinib has become approved by the FDA as of 02/17/2015 for thyroid cancer.
1. Cancer.org. What are the key statistics about thyroid cancer?. 2015. Available at: http://www.cancer.org/cancer/thyroidcancer/detailedguide/thyroid-cancer-key-statistics. Accessed February 18, 2015.
2. Medscape.com. Managing Radioactive Iodine-Refractory Thyroid Cancer. 2015. Available at: http://www.medscape.com/viewarticle/824261. Accessed February 18, 2015.
3. Glen H, Mason S, Patel H, Macleod K, Brunton VG. E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion. BMC Cancer. 2011;11:309.
4. Taylor M, Kim S, Krzyzanowska M. Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer. New England Journal of Medicine. 2015;372(7):621-630. doi:10.1056/nejmoa1406470.