Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer

Abstract

Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT population (lenvatinib, n = 261; placebo, n = 131). The primary endpoint was PFS; secondary endpoints included overall survival, overall response rate, and safety. Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib, 16.5 months; placebo, 3.7 months), although significance was not reached, presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10-1.57; P = 0.067). Overall response rates were 63.3% and 0% for lenvatinib and placebo, respectively. No significant difference was found in overall survival. The lenvatinib safety profile was similar between the Japanese and overall SELECT population, except for higher incidences of hypertension (any grade: Japanese, 87%; overall, 68%; grade ≥3: Japanese, 80%; overall, 42%), palmar-plantar erythrodysesthesia syndrome (any grade: Japanese, 70%; overall, 32%; grade ≥3: Japanese, 3%; overall, 3%), and proteinuria (any grade: Japanese, 63%; overall, 31%; grade ≥3: Japanese, 20%; overall, 10%). Japanese patients had more dose reductions (Japanese, 90%; overall, 67.8%), but fewer discontinuations due to adverse events (Japanese, 3.3%; overall, 14.2%). There was no difference in lenvatinib exposure between the Japanese and overall SELECT populations after adjusting for body weight. In Japanese patients with radioiodine-refractory differentiated thyroid cancer, lenvatinib showed similar clinical outcomes to the overall SELECT population. Some differences in adverse event frequencies and dose modifications were observed. Clinical trial registration no.: NCT01321554.

Keywords: Japanese patients; lenvatinib; progression-free survival; thyroid cancer; treatment efficacy.

Figure 1

Progression‐free survival rates of overall patients with radioiodine‐refractory differentiated thyroid cancer and the Japanese subgroup who participated in the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. Kaplan–Meier estimate of progression‐free survival in patients treated with lenvatinib (Japanese, n = 30; overall, n = 261) or placebo (Japanese, n = 10; overall, n = 131). CI, confidence interval; HR, hazard ratio; NE, not estimable.

Figure 2

Overall response and overall survival rates of overall patients with radioiodine‐refractory differentiated thyroid cancer and the Japanese subgroup who participated in the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. (a) Kaplan–Meier plot of overall survival adjusted with the rank‐preserving structural failure time model in patients treated with lenvatinib (Japanese, n = 30; overall, n = 261) or placebo (Japanese, n = 10; overall, n = 131). (b) Waterfall graph of maximum percentage change in summed longest diameter of target lesions from baseline to nadir in Japanese patients treated with lenvatinib (n = 30) or placebo (n = 10). Best overall responses in patients were categorized as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not estimable (NE). CI, confidence interval.

Figure 3

Pharmacokinetic assessments evaluating lenvatinib exposure in Japanese patients versus the overall study population with radioiodine‐refractory differentiated thyroid cancer who participated in the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. (a) Scatterplot of model‐predicted lenvatinib clearance and exposure versus body weight in Japanese patients (n = 30) versus the remainder of the overall study population (n = 230). (b) Relationship between model‐predicted lenvatinib exposure and Japanese race. Lenvatinib exposure was evaluated in Japanese patients (n = 30) versus the remainder of the overall study population (non‐Japanese patients [n = 230]). AUC, area under the curve.