Everolimus Improves Progression-Free Survival in Carcinoid Tumors

Carcinoid tumors of the lung and gastrointestinal (GI) tract are rare. Despite an often indolent natural history, when these well-differentiated neuroendocrine tumors progress on somatostatin analogue therapy, there are limited treatment options.

Investigators now report results of the RADIANT-4 trial, an industry-sponsored, international, randomized, double-blind, placebo-controlled trial of the mTOR inhibitor everolimus in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors of the lung or GI tract. Patients were randomized 2:1 to everolimus (10 mg orally daily) versus placebo. Most patients had GI primary tumors (55%–57%), were more than 18 months out from diagnosis (62%), had liver metastases (78%–80%), and had received prior somatostatin analogue therapy (53%–56%).

Progression-free survival, the primary endpoint, was significantly improved with everolimus versus placebo (11.0 vs. 3.6 months; hazard ratio, 0.48; P<0.00001). Overall survival trended superior for everolimus (23.7 vs. 16.5 months). Limited responses were seen with everolimus, but disease control was higher compared with placebo. No new safety signals were seen. Expected drug-related grade 3 or 4 adverse events were seen, including stomatitis (9%), diarrhea (7%), fatigue (3%), and infection (7%).