BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations,
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in . But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12; ).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger . Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.