Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive gastrointestinal or lung neuroendocrine tumors, a study published in the The Lancet has shown.1
Because there are limited effective systemic therapies for patients with advanced, progressive neuroendocrine tumors of the lung or gastrointestinal tract, researchers sought to evaluate the safety and efficacy of everolimus compared with placebo as a potential treatment strategy in this patient population.
For the international, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, researchers enrolled 302 patients with advanced, progressive, well-differentiated, non-functional neuroendocrine tumors of the lung or gastrointestinal tract. Participants were randomly assigned 2:1 to receive everolimus 10 mg orally daily or placebo, in addition to supportive care.
Results showed that median progression-free survival was 11.0 months (95% CI, 9.2 – 13.3) in the everolimus arm and 3.9 months (95% CI, 3.6 – 7.4) in the placebo arm, corresponding to a 52% reduction in the estimated risk of progression or death with everolimus (HR, 0.48; 95% CI, 0.35 – 0.67; P < .00001).
Researchers also found that everolimus may be associated with an overall survival benefit as well (HR, 0.64; 95% CI, 0.40 – 1.05; P = .037), but the results of that interim analysis are not statistically significant.
In regard to safety, grade 3 or 4 everolimus-related adverse events were uncommon. Grade 3 or 4 stomatitis occurred in 9% of patients who received everolimus, diarrhea and infections each in 7%, anemia in 4%, and fatigue and hyperglycemia each in 3% of everolimus-treated patients.
“Everolimus is the first targeted agent to show robust anti-tumor activity with acceptable tolerability across a broad range of neuroendocrine tumors, including those arising from the pancreas, lung, and gastrointestinal tract,” the investigators concluded.
- Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study [published online ahead of print December 15, 2015]. Lancet. doi: 10.1016/S014906736(15)00817-X.