A Phase II Study of the Safety and Efficacy of Lenvatinib in Patients with Advanced Thyroid Cancer

Abstract

Aim: To investigate the safety and efficacy of lenvatinib in advanced thyroid cancer. Patients/methods: In this Phase II study, 51 Japanese patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC), medullary thyroid cancer (MTC) or anaplastic thyroid cancer (ATC) received once-daily lenvatinib 24 mg. The primary end point was safety. Results: All patients experienced ≥1 adverse event (AE); only one patient experienced an AE leading to discontinuation. The most common any-grade AEs were hypertension, decreased appetite, palmar-plantar erythrodysesthesia, fatigue and proteinuria. Response rates for RR-DTC: 68%; MTC: 22%; ATC: 24%. Median progression-free survival for RR-DTC: 25.8 months; MTC: 9.2 months; ATC: 7.4 months. Conclusion: Lenvatinib demonstrated a manageable safety profile, proven antitumor activity in RR-DTC and promising efficacy in MTC and ATC. Clinical trial registration: clinicaltrials.gov NCT01728623

Sequential Analysis of Neutrophil-to-lymphocyte Ratio for Differentiated Thyroid Cancer Patients Treated With Lenvatinib

“…The PFS, ORR, and DCR were also slightly better in patients with lower baseline NLR. In the phase II trial of lenvatinib, a similar non-significant trend was observed in PFS (baseline NLR ≥3 vs. <3, HR=1.67, 95%CI=0.78-3.55, p=0.18), as shown by the multivariate analysis (7). Consequently, NLR values correlate with tumor activity in RR-DTC patients, and can supportively be used as a prognostic and predictive marker for RR-DTC patients treated with lenvatinib.…”

“…The values of NLR were evaluated at four time points: 6 months before starting lenvatinib, at the start of lenvatinib treatment, at the time the patient achieved best tumor response, and at the time of disease progression. Considering previous reports, we set the cutoff value of NLR at 3 (7).…”

“…NLR was significantly elevated in ATC patients compared to PTC patients, and can therefore be used as a marker to discriminate between ATC and DTC (13). In the Japanese phase II trial of lenvatinib, NLR was higher in ATC and MTC patients than in DTC patients, and a higher pre-treatment NLR may predispose to a lower PFS following lenvatinib treatment (7). However, few studies have been reported on the changes of NLR during lenvatinib treatment in RR-DTC patients.…”

Targeting XPO1 and PAK4 in 8505C Anaplastic Thyroid Cancer Cells: Putative Implications for Overcoming Lenvatinib Therapy Resistance

“…Lenvatinib, a TKI drug, shows activity against refractory thyroid cancer. A phase II study of lenvatinib conducted in Japan has documented a median OS in patients with radioactive refractory DTC at 31.8 months (95% CI: 31.8-NR), 12.1 months (95% CI: 3.8-NR) in patients with MTC and 10.6 months (95% CI: 3.8-19.8) in patients with ATC [12]. Despite this success, a proportion of patients become refractory to lenvatinib and have no alternative therapies.…”

Genetic alterations in anaplastic thyroid carcinoma and targeted therapies (Review)

“…Lenvatinib, a newer, small-molecule VEGFR inhibitor, was tested in differentiated thyroid cancer, medullary thyroid carcinoma and ATC in a phase II study. Only 11 patients with ATC were recruited; however, the results were encouraging, with three patients exhibiting a partial response according to the Response Evaluation Criteria in Solid Tumors, seven with SD and one patient exhibiting progression of disease (71). Lenvatinib has been approved in the USA for the treatment of DTC, but it is approved for all subtypes of thyroid cancer in Japan (67).…”