Lenvatinib improves OS in older patients with differentiated thyroid cancer

Lenvatinib demonstrated higher toxicity in older patients with radioiodine-refractory differentiated thyroid cancer, according to data from a phase 3 trial.

However, the drug improved OS among older patients.

As many as 15% of differentiated thyroid cancers are resistant to radioiodine treatment or can become refractory, according to Marcia S. Brose, MD, PhD, of the department of otorhinolaryngology at the Abramson Cancer Center, University of Pennsylvania, and colleagues. However, lenvatinib and sorafenib both had yet to demonstrate an improved OS in radioiodine refractory differentiated thyroid cancer.

“We show for the first time ever that lenvatinib extends overall survival for patients with radioactive iodine-refractory thyroid cancer over 65,” Brose told HemOnc Today. “While we have suspected this is the case, this is the first we have been able to prove this in a single study. This study also shows that lenvatinib is  tolerable in patients over 65 and that the side effects are manageable, and so can be given to these patients safely with close attention to management of toxicities.”

The researchers performed a randomized, double blind phase 3 study in patients stratified by age: 65 years or younger (median age, 56), or older than 65 years (median age, 71). A total of 392 patients from 21 countries received either 24mg/day of lenvatinib (n = 261) or placebo (n = 131). PFS served as the primary outcome. Secondary outcomes included safety, objective response rate and OS.

The younger lenvatinib group demonstrated longer PFS than younger placebo patients (median 20.2 months vs. 3.2 months; HR = 0.19; 95% CI, 0.13-0.27). The older lenvatinib group also demonstrated improved PFS (16.7 months vs. 3.7 months; HR = 0.27; 95% CI, 0.17-0.43). PFS appeared similar across ages in both treatment arms.

Older lenvatinib patients demonstrated longer OS than those in the placebo group (HR = 0.53; 95% CI, 0.31-0.91).

Younger patients in the lenvatinib group had a significantly higher ORR (72% vs. 55%; P = .0038), and also demonstrated longer time to first dose reduction (3.7 vs. 1.5 months) and a lower proportion of grade 3 or higher treatment related adverse events than older patients (67% vs. 89%; P < .001).

“To our knowledge, this is the first report of an OS benefit in patients with radioiodine-refractory differentiated thyroid cancer, albeit only being demonstrated in patients aged [older than] 65 years. Older patients with differentiated thyroid cancer are often treated less aggressively than younger patients despite presenting with more advanced disease, a discrepancy in care that predicts worse survival,” the researchers wrote. “In view of our findings of improved PFS and OS (in older patients) and manageable toxicities, we contend that lenvatinib treatment should be considered as a treatment option for all patients with radioiodine-refractory differentiated thyroid cancer who fulfill eligibility criteria as used in [this study], including older patients.” – by Andy Polhamus

Disclosure: Brose reports consulting or advisory roles with AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech and Oxigene; honoraria from Bayer, Exelixis and Onyx; and research funding from Bayer, Eisai, Exelixis, Genentech and Roche.