A retrospective analysis of the efficacy and safety of everolimus in patients with unresectable tumor

Everolimus is a mammalian target of rapamycin inhibitor, which is used for the treatment of patients with unresectable or metastatic renal cell carcinoma (RCC) or pancreatic neuroendocrine tumor (pNET). Severe adverse events, such as drug-induced pneumonitis, severe infection and thromboembolism, have been reported in some clinical trials. The purpose of this study was to verify the efficacy and safety of everolimus for Japanese patients in a daily practice. We retrospectively analyzed 2 patients with unresectable RCC and 6 patients with unresectable pNET, who had taken everolimus orally in Tohoku University Hospital between April, 2012 and December, 2014. Mean age of the patients was 59.5 years old and 4 patients (50%) were male. Median time to failure was 570 days in RCC patients and 97 days in NET patients. Best overall responses were PR (n = 1) and SD (n = 1) in RCC, and SD (n = 4), PD (n = 1) with 1 patient before the response evaluation in pNET. Major adverse events (≥grade 2) were observed in 7 patients (88%), including platelet count decreased (n = 2), elevation of liver enzyme (n = 2). Pneumonitis (grade 1) was observed in two patients. Severe adverse events (≥grade 3) were seen in 5 patients (63%), including platelet count decreased (n = 2), neutropenia (n = 1), elevation of liver enzyme (n = 1), hypoalbminemia (n = 1), DIC (n = 1) and pneumocystis pneumonia (n = 1). As a whole, in our cohort of patients, the treatment with everolimus was enough effective and tolerable, although it should be noted that the patient who developed pneumocystis pneumonia did not respond to antibiotics and steroid pulse therapy, and finally died 25 days later because of respiratory failure. In conclusion, our results emphasize that everolimus is a useful treatment option also in Japanese population but should be performed with careful attention to severe toxicities including fatal infections.