Lenvatinib Extended Progression-Free Survival in Patients With Metastasis

Patients in a lenvatinib treatment arm with radioiodine-refractory differentiated thyroid cancer and certain metastasis experienced a much better overall median progression-free survival compared with a placebo arm.

Mouhammed Amir Habra, MD

Patients in a lenvatinib treatment arm with radioiodine-refractory differentiated thyroid cancer (DTC) and ≥1 metastasis experienced an overall median progression-free survival (PFS) of 18.3 months compared with 3.6 months in a placebo arm (HR, 0.21; 99% CI, 0.14-0.31;P< .001), according to study results presented October 19, 2015, at the 85thAnnual Meeting of the ATA in Buena Vista, Florida.

Mouhammed A. Habra, MD, University of Texas MD Anderson Cancer Center, emphasized in the presentation that lenvatinib consistently exerted effective therapeutic benefit in the treatment of refractory DTC across all metastasis sites examined thus far.

The double-blind, placebo-controlled phase III clinical study involved 388 patients. Approximately 99% (399 of 392) of patients participating in this study had more than one metastasis site (1 site, n = 96; 2 sites, n = 134; 3 sites, n = 107, 4 sites, n = 51). Patients were randomized 2:1 for treatment with 24-mg lenvatinib daily or placebo.

Subanalysis was designed to address the question of whether or not the metastasis site can affect the outcome after lenvatinib treatment. The subanalysis focused on the most common sites of metastases: lung, bone, brain, liver, and lymph nodes, respectively. Lung (n = 350) metastases were 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 low sample size for patients with radioiodine-refractory DTC also involving brain metastasis precluded the generation of statistically significant results for brain metastasis.

Patients with bone marrow metastases constituted the lowest of all metastasis types in the study. These patients had a median PFS of 2.1 months (95% CI, 0.15-0.29). Median PFS for patients administered placebo who had radioiodine-refractory DTC and lung metastasis (95% CI, 0.16-0.42) or lymph metastasis (95% CI, 0.16-0.36) was 3.6 months. Median PFS was 3.7 months for patients with liver or brain metastasis (95% CI; 0.27-0.97 for liver; 0.14-7.1 for brain). Median PFS ranged from 3.6 to 3.7 months for nonbone metastasis. Median PFS for patients with radioiodine-refractory DTC with bone metastasis was 2.1 months. Progression free survival referred to target or non-target lesions.

Lenvatinib treatment significantly extended median PFS much longer than the 2.1 to 3.7 month range previously described for patients given placebo. Median PFS for patients treated with lenvatinib was the extended to the greatest extent in patients with lung metastasis. These patients had a median PFS of 18.7 months (95% CI, 0.15-0.29). PFS benefits were seen in patients administered lenvatinib with all examined types of metastasis except brain (14.8, 7.6, and 8.8 for lung, bone, liver, and brain subgroups, respectively).

Lenvatinib response rates were >50% for all metastasis types in patients with radioiodine- refractory DTC, with 68.1% in lung (154 of 226 patients) and 65.2% in lymph nodes (90 of 138 patients). Response rates for bone metastasis and liver metastasis were just over 50%.

“Patients with more than one type of disease at baseline had benefits similar to patient with two or more types of disease,” Habra concluded. “Benefits were preserved even in patients with multiple types of disease.”

Habra M. 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 the 85thAnnual Meeting of the ATA. October 19, 2015; Buena Vista, FL. Oral presentation.