Everolimus for Tumors Associated with Carcinoid Syndrome

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The combination of everolimus (Afinitor) plus octreotide (Sandostatin) long-acting repeatable (LAR) formulation improved progression-free survival by 23% over placebo plus octreotide LAR in a randomized phase III study of patients with advanced neuroendocrine tumors associated with carcinoid syndrome. The combination treatment was associated with a “clinically meaningful” 5.1-month increase in median progression-free survival—16.4 vs 11.3 months in patients receiving placebo—investigators for the RADIANT-2 study stated in The Lancet. “Consistent with these findings, treatment with everolimus plus octreotide LAR was associated with tumour shrinkage and stabilisation and significant reduction in biochemical markers of neuroendocrine tumours,” the investigators added.

The study enrolled 429 patients from the United States, Canada, and several other countries. All patients were aged 18 years or older, had low-grade or intermediate-grade advanced (unresectable locally advanced or distant metastatic) neuroendocrine tumours, disease progression, and a history of secretory symptoms (diarrhea or flushing) attributable to carcinoid syndrome. Researchers randomly assigned participants to receive treatment with 10 mg oral everolimus once daily or matching placebo, as well as intramuscular 30 mg octreotide LAR every 28 days.

Treatment continued until disease progression (which occurred in 95 of the 215 patients receiving everolimus and 146 of the 211 patients receiving placebo), withdrawal from treatment because of adverse events, or withdrawal of consent. The most commonly reported adverse events leading to discontinuation of treatment with everolimus plus octreotide were fatigue, diarrhea, general physical health deterioration, interstitial lung disease, and pneumonia, each occurring in 2% of patients.

‘Worthwhile Advance’

Our findings showing the efficacy of everolimus plus octreotide LAR in advanced neuroendocrine tumours are important because of the lack of effective anticancer treatment options,” the authors concluded. “Efficacy of everolimus in this population will need confirmation in a future study. Together with clear evidence of benefit from the recently completed RADIANT-3 trial of everolimus in patients with advanced pancreatic neuroendocrine tumours, our data support the efficacy of everolimus in a broad spectrum of advanced neuroendocrine tumours.

The addition of everolimus to octreotide LAR “does seem to be a worthwhile advance,” according to an accompanying commentary on the study report. “The benefit shown was somewhat compromised by an imbalance between groups, with the everolimus group containing more patients with worse performance status, more lung neuroendocrine tumours, and more patients who had received chemotherapy,” the commentators stated. They pointed out that “toxic effects related to everolimus are not insignificant,” and because of crossover, “we do not know the survival benefit.” ■

Pavel ME, et al: Lancet 378:2005-2012, 2011.

Rindi G, Caplin M: Lancet 378:1978-1980, 2011.




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