AUTHOR=Wang Wenda , Guo Gang , Shi Guohai , Wei Xin , Hu Zhiquan , Li Hanzhong , Zhang Xu , Ye Dingwei , Zhang Yushi 

TITLE=A Multi-Centric Study Assessing Safety and Efficacy of Everolimus in Adult Chinese Patients With Tuberous Sclerosis Complex Associated Renal Angiomyolipomas

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.871723

DOI=10.3389/fonc.2022.871723

ISSN=2234-943X

ABSTRACT=Background: Everolimus has been approved in China for adult patients with TSL-AML not requiring immediate surgery and has been previously shown to be an effective treatment option for TSL-AML in the Chinese population.
Methods: This 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.
Results: Treatment 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 reduction in sum of target AML volume was −56.60%, which further increased to -59.96% at Week 24 (n=38), to reach −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 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.
Conclusions: Based 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.