421P - A multicenter, randomized, double-blind, placebo (PBO)-controlled, phase III trial of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in China

Background

LEN is a multikinase inhibitor of VEGFRs 1–3, FGFRs 1–4, PDGFRα, RET, and KIT that resulted in significantly prolonged progression-free survival (PFS) compared with PBO in pts with RR-DTC in a phase III study (SELECT). However, SELECT did not include pts from China. As data in Chinese pts are required for approval of LEN for RR-DTC in China, we conducted a phase III study of RR-DTC treated with LEN vs PBO in Chinese pts.

Methods

This randomized, multicenter, double-blind, PBO-controlled study enrolled pts aged ≥18 years with RR-DTC and confirmed disease progression in the past 12 months. Pts were stratified by tumor subtype (papillary or follicular), number of prior VEGF/VEGFR-targeted therapies (0 or 1), and age (≤65 years or >65 years). LEN starting dose was 24 mg/day. The primary endpoint was PFS by independent imaging review based on RECIST v1.1. A one-sided significance level of 0.01 was utilized in the planned interim analysis. Secondary endpoints included overall response rate (ORR), overall survival, and safety.

Results

Overall, 151 Chinese pts (median age, 60 years; 52% men) were randomized 2:1 (LEN, n = 103; PBO, n = 48). At the recommendation of the Independent Data Monitoring Committee at the time of the interim analysis, the randomization phase of this study was stopped early because of positive efficacy and we conducted the primary analysis using the interim analysis cutoff date. In the LEN and PBO arms, the median durations of follow-up were 14.8 and 15.6 months, respectively. PFS was significantly improved with LEN (median 23.9 months; 95% CI 12.9–not estimable) vs PBO (median 3.7 months; 95% CI 1.9–5.6) (hazard ratio = 0.16, 95% CI 0.10–0.26; P < 0.0001 [logrank]). ORR was 69.9% with LEN and 0% with PBO. The most common treatment-related grade ≥3 adverse events (LEN, PBO) were hypertension (62.1%, 4.2%), proteinuria (23.3%, 0%), and palmar-plantar erythrodysesthesia syndrome (9.7%, 0%).

Conclusions

LEN significantly prolonged PFS compared with PBO in Chinese pts with RR-DTC, similar to the global phase III SELECT results. There were no new or unexpected toxicities with LEN in Chinese pts with RR-DTC.

Clinical trial identification

NCT02966093.

Editorial acknowledgement

Medical writing was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Eisai Co., Ltd., Tokyo, Japan, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA.

Funding

Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Disclosure

T. Kubota, T. Suzuki, H. Ikezawa: Full/Part-time employment: Eisai Co., Ltd. All other authors have declared no conflicts of interest.