Clinical Outcomes of Everolimus Rechallenge in Patients with Pancreatic Neuroendocrine Neoplasms with No Other Treatment Options

Simple Summary Pancreatic neuroendocrine neoplasms (PNENs) are a type of pancreatic tumor. Everolimus is an oral inhibitor of the mammalian target of rapamycin (mTOR). Although PNENs respond well to systematic treatment, including everolimus, the treatment options are often exhausted in clinical practice with the progression of the tumor. Recently, the efficacy of molecular targeted drugs, including mTOR inhibitors, has been assessed in rechallenge experiments. The efficacy and safety of rechallenge with everolimus in PNENs remains unclear. This study retrospectively evaluated the treatment outcomes of patients who received everolimus rechallenge. Everolimus rechallenge may be a drug treatment option for those with advanced PNEN for whom no other drug treatment option is available. Background: The clinical outcomes of everolimus rechallenge in patients with pancreatic neuroendocrine neoplasms (PNENs) are unknown. This study aimed to investigate the treatment outcomes and safety of everolimus rechallenge treatment with PNENs. Methods: Clinical data of everolimus-treated patients with PNENs at two institutions were collected. Patients who underwent everolimus rechallenge were included in the study. We analyzed the progression-free survival (PFS) and treatment response associated with everolimus rechallenge and the adverse events. Results: Between 2008 and 2020, 117 patients received initial treatment with everolimus, of which 14 patients received everolimus rechallenge. With regard to the grade of PNENs, there were 2 cases of G1, 11 cases of G2, and 1 case of G3. The median rechallenge PFS was 5.7 months. The objective response rate was 21.4%. the disease control rate was 71.4%. The only major grade 3 or 4 adverse event was neutropenia (n = 1, 7.1%). No other severe adverse event was observed. Conclusion: The outcomes and safety of everolimus rechallenge were verified, and it was deemed an acceptable treatment. Everolimus rechallenge may provide a new drug therapy for patients with advanced PNENs for whom no other drug treatment option is available.