Cecilia Lau, RPh, BCOP, APh, reviews the efficacy and safety data for everolimus in the treatment of NETs.
Daneng Li, MD: In terms of additional therapies, in addition to somatostatin analogue treatments, 1 of the other treatment options we frequently use for many of these neuroendocrine tumors are oral targeted-therapy agents, of which everolimus has relatively broad coverage for many of these neuroendocrine tumors.
Cecilia, can you comment on the efficacy data of everolimus for the treatment of neuroendocrine tumors, as well as possible adverse effects that we might potentially have to encounter and manage?
Cecilia Lau, RPh, BCOP, APh: Everolimus is an mTOR inhibitor, and the reason it has a role in the management of neuroendocrine tumors is because the PI3K/AKT/mTOR pathway is implicated in neuroendocrine tumors. There were 2 trials that led to the different indications of everolimus in the use of various neuroendocrine tumors. The first 1 is the RADIANT-3 trial. This is a phase 3, double-blind, placebo-controlled, randomized trial where patients with pancreatic neuroendocrine tumors were randomized to everolimus 10 mg per day vs placebo. In this trial, the progression-free survival primary end point at 18 months was 34% in the everolimus arm vs 9% in the placebo arm.
The RADIANT-4 trial, which is another phase 3 trial, was conducted in patients with nonfunctional lung or GI [gastrointestinal] and not pancreatic neuroendocrine tumor. In this trial, patients were randomized to everolimus 10 mg daily vs placebo and the median progression-free survival in this trial was 11 months for everolimus vs 3.9 months for the placebo arm.
In terms of adverse effects and things to look out for regarding everolimus and its use in patients with neuroendocrine tumors, a couple of adverse effects that would be of particular interest with these patients are the potential for hyperglycemia and diarrhea. As we mentioned earlier, these are also potential adverse effects of the somatostatin analogues, and it would not be uncommon for patients to be on both somatostatin analogues and everolimus.
In addition, everolimus has an adverse effect of stomatitis. The stomatitis is characterized by abscessed lesions or ovoid ulcers that occur in the oral cavity. It has an incidence of up to 70% all grades, and although grade 3/4 is usually under 10%, it is more likely to happen in the first 8 weeks of treatment.