Aim
In the phase 3 study of patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC), lenvatinib prolonged median progression-free survival (PFS) versus placebo (18.3 vs 3.6 months; HR: 0.21; 99% CI 0.14–0.31; P<0.001). This subanalysis examines efficacy by baseline metastasis site.
Methods
Patients with progressive RR-DTC were randomized 2:1 to lenvatinib 24 mg/day or placebo. Tumor assessments performed at baseline and every 8 weeks were independently evaluated using RECIST version 1.1.
Results
Of 392 patients, 388 (99.0%) had ≥1 metastatic site (1, n=96; 2, n=134; 3, n=107, ≥4, n=51); 34% and 66% had follicular and papillary histologies, respectively. Median PFS for patients with 1, 2, 3, and ≥4 sites was not reached; 18.3, 16.5, and 11.0 months, respectively, for lenvatinib; and 3.7, 3.7, 3.6, and 2.0 months, respectively, for placebo. Overall response rates were: brain 66.7% (6/9), bone 51.0% (53/104), liver 51.2% (22/43), lung 68.1% (154/226), and lymph node 65.2% (90/138); patients could have ≥1 metastatic site. There were 16 patients with brain (PFS for lenvatinib vs placebo: 8.8 vs 3.7 months; HR: 1.00), 376 without brain (18.7 vs. 3.6; HR: 0.21), 152 with bone (14.8 vs 2.1; HR: 0.26); 240 without bone (20.2 vs 3.7; HR: 0.18), 71 with liver (7.6 vs 3.7; HR: 0.51), 321 without liver (20.2 vs 3.6; HR: 0.17), 350 with lung (18.7 vs 3.6; HR: 0.21), 42 without lung (14.8 vs 3.6; HR: 0.24), 202 with lymph node (14.8 vs 3.6; HR: 0.24) and 190 without lymph node metastasis (not estimable vs 3.6; HR: 0.24). Differences between subgroups for lenvatinib were less evident for placebo.
Conclusion
For these metastasis sites, response rates were >50% and PFS benefit with lenvatinib was preserved in all but the brain subgroup. These findings suggest greater lenvatinib treatment benefit in patients with better prognosis, as defined by metastatic site.