Researchers at the University of Texas MD Anderson Cancer Center found that lenvatinib improves progression-free survival in patients with advanced radioiodine-refractory thyroid cancer. The results were part of a Pivotal Phase 3 randomised multicenter study led by Steven I. Sherman, M.D., associate vice-provost for Clinical Research, and professor and chair, Endocrine Neoplasia and Hormonal Disorders, MD Anderson, and were published in the New England Journal of Medicine, entitled “Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer.”
Thyroid cancer is a condition that in 2015 will affect 62,450, with an anticipated mortality of 1,950 people, according to the American Cancer Society.
“For decades, in this patient population, the treatment was often to repeat ineffective doses of radio-active iodine, and possibly salvage therapy with chemotherapy,” Dr. Sherman, the study’s senior author and the international principal investigator, said in a news release. “About 10 years ago, with the growing availability of novel targeted agents and multi-targeted kinase inhibitors, we began to recognize potential for treating this subgroup of patients with anti-angiogenic therapy and sought to enroll those with refractory disease in clinical trials.”
In the study, patients with progressive iodine-131 refractory thyroid cancer were randomly assigned into two groups: the first group included 261 patients that received a daily 24mg dose of lenvatinib for a total of 28-day cycles, while the second group included 131 patients that received a placebo. At the time of disease progression, patients who were part of the placebo group could have open-label lenvatinib.
Results revealed a median progression-free survival of 18.3 months in the group of patients that received lenvatinib, and of 3.6 months in patients who received the placebo. The response rate was of 64.8% in the group of patients that received lenvatinib, and only of 1.5% in the control group.
“In our study, we not only saw a dramatic improvement in progression-free survival, there was also a 65 percent response rate – almost unprecedented results for thyroid cancer patients with such advanced disease. We also found a strongly suggestive trend in how long patients lived, and a small number of patients had a complete response. While we couldn’t identify tumor mutations that might predict response, this represents a very exciting area of study going forward in hopes of possibly offering cure to a greater number of patients,” said Dr. Sherman.
Adverse effects occurred in 40% of patients who received lenvatinib, including hypertension, diarrhea, fatigue or asthenia, decreased appetite, decreased weight, and nausea. Withdrawals from the study due to adverse effects occured in 37 patients receiving lenvatinib and in 3 patients who received the placebo. Furthermore, of the total 20 deaths, 6 were considered drug-related in the group of patients who received lenvatinib.
“The side effect profile is actually quite typical for this class of drugs. We’ve learned over the years to be aggressive about dosing modifications and coming up with clever ways of helping patients tolerate the medication where drug effectiveness is maintained but with a minimum of those side effects. It’s paramount that patients are selected carefully and physicians giving the drug focus on symptom support,” stated Dr. Sherman.