Everolimus Improves Progression-Free Survival in Carcinoid Tumors

Summary and Comment |
January 12, 2016

Everolimus Improves Progression-Free Survival in Carcinoid Tumors

  1. David H. Ilson, MD, PhD

The mTOR inhibitor has now shown activity across the spectrum of neuroendocrine tumors.

  1. David H. Ilson, MD, PhD

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%).

Comment

Everolimus will likely become a new therapeutic option in the treatment of carcinoid tumors, well-differentiated neuroendocrine tumors of the lung and GI tract. As the authors indicate, everolimus now has shown activity across the spectrum of neuroendocrine tumors, including pancreatic neuroendocrine tumors and carcinoid tumors. Given the modest benefit seen, the molecular characterization and the study of potential biomarkers in these tumors will hopefully yield predictive factors to better select patients for this as well as other new targeted therapies.

Editor Disclosures at Time of Publication

  • Disclosures for David H. Ilson, MD, PhD at time of publication Consultant / Advisory board Amgen; Eli Lilly–ImClone; Macrogenics; Bayer Speaker’s bureau Genentech/Roche Grant / Research support Bayer; Amgen; Bristol-Myers Squibb

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