Effective Sequencing of Treatments for pNETs - Episode 7

RADIANT-3 Trial: Everolimus for Patients With pNETs

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The utilization of the mTOR inhibitor everolimus as a treatment for patients with pancreatic neuroendocrine tumors (pNET) has increased since the FDA first approved the drug in this space in 2011, based on findings from the RADIANT-3 study.

In the randomized phase III RADIANT-3 study, everolimus was compared with placebo for patients with pNETs, explains Jonathan Strosberg, MD. The median progression-free survival (PFS) was 11.0 months with everolimus compared with 4.6 months with placebo (HR = 0.35). However, Strosberg notes, the RADIANT-3 trial was designed as a crossover study that allowed patients randomized to placebo to receive everolimus following progression. As a result, an overall survival benefit was not demonstrated for everolimus.

In terms of adverse events, there were reports of mouth sores, aphthous stomatitis, skin rash, hyperglycemia, and hyperlipidemia in the study, Strosberg states. Additionally, since everolimus is an immunosuppressant, patients occasionally developed atypical infections, such as aspergillosis or pneumocystis pneumonia, although these conditions are fairly rare, Strosberg notes. A small portion of patients in the study also developed pulmonary pneumonitis.

Everolimus is efficacious in patients with pNETs, but treatment can induce unpredictable side effects, Diane Reidy-Lagunes, MD, MS, states. Some patients will have no side effects, while others may experience fatigue or mucositis. Approximately two-thirds of patients experience some form of mucositis, some of which can be debilitating. However, Reidy-Lagunes notes, these symptoms generally resolve when the dose is reduced.

The RADIANT-1 trial raised questions regarding whether prior treatment with chemotherapy impacts the effectiveness of everolimus in pNETs. In this study, patients treated with everolimus monotherapy following progression on chemotherapy had a PFS of 9.7 months compared with 16 months for untreated patients. However, a subgroup analysis of the RADIANT-3 trial showed that the responses were identical regardless of prior exposure to chemotherapy, Rodney F. Pommier, MD, notes.