Results from a sub-analysis of the impact of age on the safety and efficacy of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the randomized double-blind placebo-controlled phase III SELECT trial (ClinicalTrials.gov identifier: NCT01321554) showed that lenvatinib significantly increased progression-free survival (PFS).
Lenvatinib is a multiple kinase inhibitor against VEGFR1, VEGFR2, and VEGFR3.
In this study, 392 patients were stratified by age (65 years and younger or older than 65 years) and received 24 mg/day lenvatinib (n=261) or placebo (n=131). In both study arms stratified by age, median age in the younger group was 56 years and median age in the older group was 71 years.
Both the younger and older groups experienced significantly improved PFS with lenvatinib (20.2 months) vs placebo (3.2 months) (hazard ratio [HR], 0.19; 95% CI, 0.13 to 0.27; P <.001) in the younger group and with lenvatinib (16.7 months) vs placebo (3.7 months) (HR, 0.27; 95% CI, 0.17 to 0.43; P <.001) in the older group.
Overall survival (OS) improved in older patients receiving lenvatinib (HR, 0.53; 95% CI, 0.31 to 0.91; P =.020). Younger patients receiving lenvatinib experienced significantly improved overall response rates (72% vs 55%, P =.0038), longer time to first dose reduction (3.7 vs 1.5 months), and lower percentage of grade 3 or higher treatment-related adverse events (67% v 89%; P <.001) compared with older patients receiving lenvatinib.
Although higher toxicity was observed in older patients receiving lenvatinib, they still experienced improved PFS. Treatment crossover was allowed after progression of disease, yet the OS benefit remained in older patients receiving lenvatinib. These results suggest that lenvatinib is efficacious, with a tolerable safety profile in patients of any age with RR-DTC.
1. Brose MS, Worden FP, Newbold KL, Guo M, Hurria A. Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the phase III SELECT Trial [published online June 14, 2017]. J Clin Oncol. doi:10.1200/JCO.2016.71.6472