Lenvatinib shows promise for radioiodine-refractory, differentiated thyroid cancer
Patients with advanced, radioiodine-refractory, differentiated thyroid cancer demonstrated encouraging response rates and PFS when treated with lenvatinib, according to data from a phase 2 trial.
Lenvatinib (Lenvima, Eisai) — a multi-targeted tyrosine kinase inhibitor that targets VEGF receptors 1-3 and fibroblast growth factor receptors 1-4 —induced responses in patients who had and had not previously received VEGF therapy, results showed.
Maria E. Cabanillas
Patients with radioiodine-refractory, differentiated thyroid cancer (RR-DTC) have a 10-year survival rate of only 10% after the detection of distant metastases, according to study background. Because cytotoxic agents have a marginal effect, researchers are investigating novel targeted therapies.
Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders in the division of internal medicine at The University of Texas MD Anderson Cancer Center, and colleagues conducted this open-label, single-arm trial to determine the efficacy and safety of lenvatinib in patients with RR-DTC.
Objective response rate (ORR) served as the primary endpoint. Secondary endpoints included PFS, OS, time to response, response duration, safety and tolerability.
The researchers identified 58 patients with RR-DTC from 30 sites in six countries from October 2008 to February 2010. Patients received 24 mg lenvatinib once daily in 28-day cycles until disease progression, adverse toxicity, withdrawal or death.
After a minimum follow-up of 14 months, patients demonstrated an ORR of 50% (95% CI, 37-63), which included only partial responses. The median time to response was 3.6 months (95% CI, 1.8-3.7) and the median response duration was 12.7 months (95% CI, 8.8 to not evaluable). The median PFS was 12.6 months (95% CI, 9.9-16.1).
The ORR for the 17 patients who had previously been treated with VEGF therapy was 59% (95% CI, 33-82).
Grade 3 and 4 adverse events occurred in 72% of the patients. The most frequent events were weight loss (12%), hypertension (10%), proteinuria (10%) and diarrhea (10%). Most patients with hypertension and/or proteinuria were managed successfully without adjusting the dose of the lenvatinib.
There were three treatment-emergent deaths, including one patient who died of arterial hemorrhage and one patient who died of cardiac arrest. The researchers noted that thromboembolic events are known associates of VEGFR inhibitors and highlighted the importance of carefully screening patients to ensure only those with clinically significant disease are chosen for treatment.
“This finding may have important clinical implications because the use of VEGF [receptor]-targeted therapy in RR-DTC is likely to increase in the near future given the approval of sorafenib (Nexavar, Bayer), and lenvatinib as well as the investigation of vandetanib (Caprelsa, IPR Pharms) in a phase 3 trial for this indication,” Cabanillas and colleagues wrote. – by Anthony SanFilippo
Disclosure: The study was funded by Eisai. Cabanillas reports receiving research funding from Eisai, Exelixis, Roche and Salient, advisory board service for Eisai, Exelixis and Bayer and serving as consultant to AstraZeneca. Please see the full study for a list of all other researchers’ relevant financial disclosures.