Table_2_A Multi-Centric Study Assessing Safety and Efficacy of Everolimus in Adult Chinese Patients With Tuberous Sclerosis Complex Associated Renal Angiomyolipomas.docx

BackgroundEverolimus has been approved in China for adult patients with TSC-AML (tuberous sclerosis associated renal angiomyolipomas) not requiring immediate surgery and has been previously shown to be an effective treatment option for TSC-AML in the Chinese populationMethodsThis is an open label, single arm, multi-center Phase IV post-approval commitment study to further assess the safety and efficacy of everolimus in patients with TSC-AML who do not require immediate surgical intervention. The primary outcome was to evaluate the safety of everolimus while the secondary outcome was to evaluate AML response.ResultsTreatment with everolimus was associated with a clinically meaningful best overall AML response rate of 70% (95% CI: 53.5, 83.4). Of the 38 evaluable patients, 37 (97%) patients experienced a reduction in the sum of volumes of target angiomyolipoma lesions relative to baseline. At Week 12 (n=38), the median percentage change in sum of target AML volume was −56.60%, which further changed by -59.96% at Week 24 (n=38), and by −64.41% at Week 48 (n=22). Throughout the study, renal function remained relatively stable. Patients with TSC associated lymphangiomyomatosis (LAM) (N=13) demonstrated a lower than expected rate of decline in pulmonary function tests (PFTs). Everolimus was generally well tolerated with no significant safety findings in Chinese patients. Most of the adverse events were of grade 1-2, and manageable with appropriate dose adjustments and supportive therapies. There were no treatment discontinuation due to AE and no treatment death was reported.ConclusionsBased on the efficacy and safety data presented in this study, the overall clinical benefit/risk assessment further supports the use of everolimus as a viable treatment option for Chinese patients with TSC-AML.

背景：依维莫司已在中国获得批准，用于治疗不需要立即手术的成人TSC-AML（肾错构瘤相关肾血管肌脂瘤）患者，并且此前研究已表明其对中国人群中的TSC-AML具有有效的治疗作用。
方法：本研究是一项开放标签、单臂、多中心的四期后上市承诺研究，旨在进一步评估依维莫司在无需立即手术干预的TSC-AML患者中的安全性和有效性。主要终点是评估依维莫司的安全性，次要终点是评估AML反应。
结果：依维莫司治疗与具有临床意义的最佳总体AML反应率70%（95% CI：53.5，83.4）相关。在38名可评估的患者中，有37名（97%）患者的目标血管肌脂瘤病变体积总和相对于基线有所减少。在第12周（n=38）时，目标AML体积总和的中位百分比变化为-56.60%，在第24周（n=38）进一步变化为-59.96%，在第48周（n=22）变化为-64.41%。在整个研究过程中，肾功能保持相对稳定。伴有TSC相关淋巴管平滑肌脂肪瘤（LAM）的患者（N=13）在肺功能测试（PFTs）中的下降率低于预期。依维莫司在中国患者中通常耐受性良好，未发现显著的安全问题。大多数不良事件为1-2级，可通过适当的剂量调整和支持性治疗管理。没有因不良事件而终止治疗，也没有报告治疗死亡。
结论：基于本研究呈现的有效性和安全性数据，总体临床益处/风险评估进一步支持依维莫司作为中国TSC-AML患者可行治疗选择的立场。