Lenvatinib PFS Benefit in DTC Maintained Across Metastasis Sites

Published: Wednesday, Oct 21, 2015

Mouhammed Amir Habra, MD

Mouhammed Amir Habra, MD

The progression-free survival (PFS) benefit with lenvatinib in radioactive iodine (RAI)-refractory (R) differentiated thyroid cancer (DTC) was observed across common sites of metastasis, according to a subanalysis of the phase III SELECT trial.

However, the data, which were presented at the 2015 International Thyroid Congress, showed that lenvatinib did not reduce the risk of disease progression in patients with brain metastasis.

“Ongoing data analyses of the phase III SELECT trial provide further understanding of the effect of lenvatinib in patients with locally recurrent or metastatic, progressive RAI-R DTC,” Mouhammed Amir Habra, MD, lead author of the subanalysis, said in a statement.

“This continued analysis will be important for both oncologists and endocrinologists as they work to treat patients with this difficult-to-treat form of thyroid cancer," added Habra, who is an associate professor in the Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, at The University of Texas MD Anderson Cancer Center.

Earlier this year, the FDA approved the multikinase inhibitor lenvatinib for patients with RAI-R DTC based on data from the double-blind, placebo-controlled SELECT trial. The study randomized 392 patients with advanced RAI-refractory DTC in a 2:1 ratio to oral lenvatinib at 24-mg daily in 28-day cycles (n = 262) or placebo (n = 131). Pretreatment with one prior TKI regimen was allowed. Tumors were assessed per RECIST 1.1 at baseline and every 8 weeks following randomization.

Treatment with lenvatinib reduced the risk of disease progression by 79% (HR, 0.21; 99% CI, 0.14-0.31; P <.0001). At a median treatment duration of 13.8 months with lenvatinib and 3.9 months with placebo, the median progression-free survival was 18.3 months versus 3.6 months, respectively. The objective response rate with lenvatinib was 64.8% versus 1.5% with placebo. The subanalysis was designed to address the question of whether or not the metastasis site affects the outcome after lenvatinib treatment. Ninety-nine percent of patients enrolled in the trial (n = 388) had at least 1 site of metastasis (1 site, n = 96; 2 sites, n = 134; 3 sites, n = 107, ≥4 sites, n = 51).

Median PFS was improved with lenvatinib versus placebo, regardless of the number of metastasis sites: 1 site (not reached vs 3.7 months), 2 sites (18.3 vs 3.7 months), 3 sites (16.5 vs 3.6 months) and ≥4 sites (11.0 vs 2.0 months).

Lung (n = 350) metastases were the most common among the metastasis subgroups, followed by bone metastasis (n = 152), liver metastasis (n = 71), lymph node metastasis (n = 202), and brain metastasis (n = 16). The overall response rates in these subgroups were 68.1%, 51.0%, 51.2%, 65.2%, and 66.7%, respectively.

The HR for PFS held up across 4 of the 5 subgroups: bone (HR, 0.26; median PFS = 14.8 vs 2.1 months); liver (HR, 0.51; 7.6 vs 3.7 months); lung (HR, 0.21; 18.7 vs 3.6 months); and lymph node (HR, 0.24; 14.8 vs 3.6 months).

For patients with brain metastases, there was a numerical improvement in PFS (8.8 vs 3.7 months) however, the HR was 1.00. The low sample size for patents with brain metastases may have precluded the generation of statistically significant results for this population.

In there abstract conclusion, Habra et al wrote, “These findings suggest a greater lenvatinib treatment benefit in patients with better prognosis, as defined by metastatic site.”


Habra MA, Song J, Rietschel P, et al. Outcomes by site of metastasis for patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib versus placebo: results from a phase 3 randomized trial. Presented at: 2015 International Thyroid Congress; October 18-23, 2015; Orlando, FL. Abstract 55.


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