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 vs 2.7% (n=103) for placebo in lung (P < 0.0001), –35.6% (n=14) vs 5.1% (n=12) in liver (P < 0.0001), –47.5% (n=119) vs –2.9% (n=55) in lymph node (P < 0.0001), and –10.7% (n=34) vs 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.