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Lenvatinib improved PFS in radioiodine-resistant differentiated thyroid cancer
CHICAGO — The oral multityrosine kinase inhibitor lenvatinib significantly prolonged PFS compared with placebo in patients with differentiated thyroid cancer who were resistant to standard radioiodine therapy, according to results of a randomized phase 3 study presented at the ASCO Annual Meeting.
Lenvatinib (E7080, Eisai) — which inhibits VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor alpha, RET and KIT signaling networks — also demonstrated a manageable toxicity profile, researchers said.
“Patients with thyroid carcinoma with refractory disease at the metastatic stage have a poor survival rate, with only 10% alive at 10 years,” researcher Martin Schlumberger, MD, professor of oncology at the University Paris Sud in Paris, France, said during a press conference. “Until very recently, there were very few therapeutic options for these patients.”
The SELECT trial included 392 patients who had progressed within 13 months of previous treatment. Median patient age was 63 years and 51% were male.
Schlumberger and colleagues randomly assigned patients 2:1 to daily 24 mg lenvatinib or placebo. Treatment was administered in 28-day cycles.
Median OS had not been reached at the time of analysis; however, a greater proportion of patients died in the placebo arm than in the lenvatinib arm (35.9% vs. 27.2%).
Patients assigned lenvatinib demonstrated significantly longer median PFS (18.3 months vs. 3.6 months; HR=0.21; 95% CI, 0.14-0.31).
Subgroup analyses indicated lenvatinib significantly extended median PFS among the 66 patients who had previously received VEGF-targeted therapy (15.1 months), as well as among the 195 patients who had not (18.7 months).
Four patients (1.5%) achieved a complete response with lenvatinib, compared with no patients in the placebo arm. Researchers observed partial responses in 63.2% (n=165) of patients assigned lenvatinib and 1.5% (n=2) of patients assigned placebo.
The median time to response with lenvatinib was 2.0 months. Researchers reported longer median treatment duration in the lenvatinib arm (13.8 months vs. 3.9 months).
Any-grade adverse events associated with lenvatinib included hypertension (68%), diarrhea (59%), decreased appetite (50%), weight loss (46%) and nausea (41%). Grade ≥3 adverse events associated with treatment included hypertension (42%), proteinuria (10%), weight loss (10%), diarrhea (8%) and decreased appetite (5%).
A majority of patients assigned lenvatinib (78.5%) received dose reductions, and 14.2% discontinued treatment due to an adverse event.
Twenty fatal events occurred, six of which were treatment-related. Researchers are continuing to investigate the causes of these deaths, Schlumberger said.
“We are confident that, based on our findings, lenvatinib will eventually become a standard treatment for radioiodine-resistant thyroid cancer,” Schlumberger said in a press release. “As little as a year ago, this group of patients had no effective treatment options. It’s remarkable that we now have two active drugs in this setting, both of them tyrosine kinase inhibitors.”
For more information:
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Schlumberger M. Abstract #LBA6008. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.
Disclosure: The study was funded by Eisai Inc. The researchers report consultant/advisory roles with, employment/leadership positions with, and honoraria or research funding from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Exelixis, Genzyme, Il Dong Pharmaceuticals, Merck Serono, Novartis, Onyx, Pfizer, Roche and Sanofi.