Responses in specific metastases following treatment with lenvatinib (LN): Results from the phase 3 SELECT trial

Abstract

Aim: Lenvatinib, a multikinase inhibitor, significantly prolonged median progression-free survival versus placebo in the phase 3 SELECT study of patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC; 18.3 vs 3.6 months; hazard ratio [HR]: 0.21; 99% confidence interval [CI]: 0.14-0.31; P < 0.001). Because metastatic RR-DTC is associated with poor overall survival, this subanalysis examined response in specific metastasis sites. Methods: Patients were randomized 2:1 to lenvatinib 24 mg/day or placebo. Tumor assessments in lung, liver, lymph nodes and bone were evaluated by independent radiologic review using Response Evaluation Criteria in Solid Tumors version 1.1 at baseline and 8-week intervals. Results: Lenvatinib-treated patients showed tumor shrinkage in all targeted sites. Mean change in tumor size from baseline in mm for lenvatinib and placebo, respectively, was 35.0 (n = 199) and 36.5 (n = 107) in lung, 47.6 (n = 15) and 54.9 (n = 12) in liver, -37.5 (n = 126) and 39.8 (n = 57) in lymph node and 65.9 (n = 41) and 63.1 (n = 17) in bone metastases. Mean maximum percent change from baseline was -45.9% (n = 189) for lenvatinib versus 2.7% (n = 103) for placebo in lung (P < 0.0001), -35.6% (n = 14) versus 5.1% (n = 12) in liver (P < 0.0001), -47.5% (n = 119) versus -2.9% (n = 55) in lymph node (P < 0.0001) and -10.7% (n = 34) versus 6.5% (n = 16) in bone metastases (P < 0.01). In the lenvatinib arm, median duration of objective response was not estimable (NE; 95% CI: 16.6-NE; n = 139), 7.3 (1.9-NE; n = 7), 16.8 (95% CI 12.9-NE; n = 84), and 12.9 (95% CI 3.6-NE; n = 10) months for patients with lung, liver, lymph node and bone metastases, respectively. Conclusions: In targeted metastasis sites, greater tumor shrinkage was observed following lenvatinib treatment versus placebo. These data provide additional evidence for the clinical benefit of lenvatinib treatment for RR-DTC, particularly in patients with specific metastases, although responses are also observed in patients with bone metastases.