The FDA has granted approval to Lenvima (lenvatinib) as a treatment for patients with progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), based on findings from the phase 3 SELECT trial.
BY Jason M. Broderick
The Food and Drug Administration (FDA) has granted approval to Lenvima (lenvatinib) as a treatment for patients with progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), based on findings from the phase 3 SELECT trial. The approval comes two months ahead of the FDA's scheduled decision date.
[Read "Lenvatinib Approval for Thyroid Cancer “Likely” as FDA Decision Date Nears
In the SELECT trial, treatment with the multikinase inhibitor Lenvima reduced the risk of disease progression by 79 percent. The SELECT trial randomized 392 patients with advanced RAI-refractory DTC in a 2:1 ratio to oral Lenvima or placebo. Pretreatment with one prior tyrosine kinase inhibitor regimen was allowed. At a median treatment duration of 13.8 months with Lenvima and 3.9 months with placebo, the median progression-free survival was 18.3 months versus 3.6 months, respectively.
The objective response rate with Lenvima was 64.8 percent versus 1.5 percent with placebo. Four patients in the Lenvima arm had complete responses versus none in the placebo group, with partial responses in 165 and 2 patients, respectively.
“I think based on the results of this study, that this could become the drug of choice for first-line therapy for patients with progressive, radioactive iodine-refractory, differentiated thyroid cancer,” said the senior investigator of SELECT, said Steven I. Sherman, professor and chair of Endocrine Neoplasia and Hormonal Disorders at MD Anderson Cancer Center. “The adverse events that were seen were fairly typical of what has been seen in the earlier studies with lenvatinib and anticipated for other antiangiogenic drugs.”
Specifically, 97.3 percent of patients receiving Lenvima and 59.5 percent of patients on placebo experienced a treatment-related adverse event. The most frequently reported events, moderate to severe in nature, included hypertension (42.9 percent), proteinuria (10 percent), decreased weight (9.6 percent), fatigue (9.2 percent) and diarrhea (8 percent).
Sherman also noted it was significant that the rate of moderate to severe palmar–plantar erythrodysesthesia syndrome was 3.4 percent. He said that Nexavar (sorafenib), the other TKI approved in this setting in recent years, “had a very high frequency of palmar-plantar erythrodysesthesia in the pivotal phase 3 DECISION study.”
There were six patient deaths in the Lenvima arm considered to be treatment related, including pulmonary embolism, one hemorrhagic stroke, one related to a general deterioration of health, and three in which no specific cause was identified.
Martin Schlumberger, lead author of the SELECT trial, commented on these treatment-related deaths in an interview at the 2014 ASCO Annual Meeting. “These six deaths are too many, but we have to compare that to the hundreds of lives that were saved from treatment with the drug. So you have efficacy, but you also have toxicities and usually these go together,” said Schlumberger, a professor of oncology at the University Paris Sud in Paris, France.
With Nexavar and Lenvima both now both available for RAI-refractory DTC, the issue of sequencing now arises. Sherman, for his part, said he would use Lenvima first. “The degree of improvement and progression-free survival would appear to be markedly higher with lenvatinib than sorafenib. So I personally think that the effectiveness of lenvatinib is going to be superior to that of sorafenib in this patient cohort.”
Schlumberger, however, did not express a first-line preference.
“When patients with distant metastasis or locally advanced disease progress, they progress slowly so they can be treated with one of these two drugs. Some will respond and then progress but still be alive and in good condition. So most of these patients will require two lines of treatment. So we may start with sorafenib, or we may start with lenvatinib but in the end they will receive both drugs.”