Lessons learned: The combination of everolimus and low-dose prednisone administered daily was hypothesized to prevent noninfectious pneumonitis (NIP) and mucositis, two common adverse events related to everolimus. Although mucositis was detected in only one case, all-grade NIP occurred in four of eight cases (50%), and this was considered enough to stop accrual of the study.These data suggest the need for careful monitoring of patients receiving everolimus who are treated with corticosteroids.
Background: Everolimus is standard of care in the treatment of patients affected by metastatic renal cell carcinoma (mRCC) that has progressed after at least one previous line of treatment. Stomatitis and noninfectious pneumonitis (NIP) are common adverse events (AEs) in patients treated with everolimus. Prednisone could reduce the incidence of stomatitis, and it is commonly used to treat NIP. We hypothesized that low doses of prednisone could reduce the incidence and/or the severity of everolimus-induced NIP and stomatitis.
Methods: We have conducted an open-label, single-arm, phase II trial of prednisone 5 mg b.i.d. added to everolimus 10 mg/day in patients with mRCC. We planned to evaluate the safety, tolerability, and activity of this combination in mRCC patients. We aimed to reduce incidence of drug discontinuations due to stomatitis or NIP from 25% to 10%.
Results: Three (38%) of the first eight patients enrolled experienced grade ≥2 pneumonitis and stopped treatment. Grade 1 stomatitis occurred in only one patient (13%). Five of eight patients experienced disease progression at the 2-month evaluation. Two patients (25%) were reported free of disease progression at 1 year of treatment.
Conclusion: The incidence of NIP in these patients was considered too high for completing accrual of this study. These results may be of interest for investigating the pathogenesis of NIP and suggest that patients should be carefully followed if treated with chronic corticosteroids while receiving everolimus.
经验总结
• 假设依维莫司联合低剂量泼尼松每日给药可预防与依维莫司相关的两种常见不良事件, 即非感染性肺炎（NIP）和黏膜炎。虽然仅在单个病例中观察到黏膜炎, 但8例病例中有4例（50%）出现了各种级别的NIP, 认为足以根据该结果停止研究招募。
• 这些数据表明, 需要密切监测使用皮质类固醇的依维莫司治疗患者。
摘要
背景. 依维莫司是既往至少接受一线治疗后疾病进展的转移性肾细胞癌（mRCC）患者的标准治疗药物。口腔炎和非感染性肺炎（NIP）是依维莫司治疗患者中的常见不良事件（AE）。泼尼松可降低口腔炎的发生率, 并且其也常用于治疗NIP。我们假设低剂量泼尼松可降低依维莫司引起的NIP和口腔炎的发生率和/或严重程度。
方法. 我们进行了一项开放性、单臂、II期临床试验, mRCC患者在试验中接受泼尼松5mg b.i.d与依维莫司10mg/日联合治疗。计划在mRCC患者中评价这一联合治疗方案的安全性、耐受性和疗效。本试验的目标是将口腔炎或NIP导致的停药率从25%降至10%。
结果. 最先入组的8例患者中有3例（38%）出现≥2级肺炎并停止治疗。仅1例患者（13%）出现1级口腔炎。2个月时的评价结果显示, 8例患者中有5例出现疾病进展。报告称治疗1年时2例患者（25%）无疾病进展。
结论. 这8例患者中的NIP发生率过高, 故无法按计划完成研究招募。这些结果对于NIP发病机制的研究可能具有重要意义, 且提示我们应密切随访在依维莫司治疗期间长期使用皮质类固醇的患者。
Trial registration: ClinicalTrials.gov NCT02479490.
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