Everolimus for pNETs and Carcinoid Tumors

Everolimus, an mTOR inhibitor, and sunitinib, an antiangiogenic tyrosine kinase inhibitor, have been shown to extend time to progression in patients with metastatic pancreatic neuroendocrine tumors (pNETs). These agents are typically used in individuals who have progressed while on somatostatin analogs, states Jonathan R. Strosberg, MD, which are the first-line treatment of choice for most well differentiated tumors that are not too clinically aggressive.

Aphthous stomatitis is the most common toxicity with everolimus, and can be managed with steroid paste or mouthwash. Everolimus may also cause pneumonitis, which can range from mild inflammation and cough to significant cough and dyspnea. Dose reductions or treatment breaks may be appropriate strategies in more severe situations. The typical starting dose of everolimus is 10 mg daily, while dose reductions to 7.5 mg or 5 mg daily can occur, comments Strosberg.

Response to treatment can be assessed in various ways, such as radiographically through scans, biochemically with tumor markers, or clinically, using symptom improvement. Treatment with everolimus is often continued until evidence of disease progression, as there is no concern of cumulative toxicity, explains James C. Yao, MD. Yao’s practice repeats anatomic CT or MRI scans every 3 months to verify whether current treatment is still effective.

Recent data from the RADIANT-4 study showed that patients with advanced carcinoid tumors in the gastrointestinal tract or lung benefited from treatment with everolimus compared with placebo, with a significant improvement in progression-free survival, explains Matthew H. Kulke, MD. This suggests that everolimus may be effective in treating not only pNETs but other types of NETs as well, he adds.