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Genomic Profiling and Response to Immune Checkpoint Inhibition plus Tyrosine Kinase Inhibition in FH-Deficient Renal Cell Carcinoma.
Xu, Yunze; Kong, Wen; Cao, Ming; Wang, Jieying; Wang, Zaoyu; Zheng, Liang; Wu, Xiaoyu; Cheng, Rongrong; He, Wei; Yang, Bo; Dong, Baijun; Pan, Jiahua; Chen, Yonghui; Huang, Jiwei; Jiang, Chen; Zhai, Wei; Li, Fangzhou; Chen, Ruohua; Zhou, Xiang; Wu, Guangyu; Geng, Xiaochuan; Chen, Jiasheng; An, Huimin; Yuan, Yichu; Xu, Tianyuan; Chen, Dongning; Lin, Dengqiang; Xu, Lieyu; Huang, Kangbo; Peng, Ling; Yu, Yanfei; Tai, Shengcheng; Qi, Honggang; Luo, Kai; Kang, Xiaonan; Wang, Hang; Huang, Yiran; Zhang, Jin; Xue, Wei.
Afiliación
  • Xu Y; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Kong W; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Cao M; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Wang J; Clinical Center for Investigation, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Wang Z; Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Zheng L; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Wu X; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Cheng R; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • He W; Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yang B; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Dong B; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Pan J; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Chen Y; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Huang J; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Jiang C; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Zhai W; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Li F; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Chen R; Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Zhou X; Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Wu G; Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Geng X; Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Chen J; Department of Urology, Changzhou No. 2 People's Hospital, Changzhou, China.
  • An H; Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yuan Y; Department of Urology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xu T; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Chen D; Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
  • Lin D; Department of Urology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.
  • Xu L; Department of Urological Surgery, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China.
  • Huang K; Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Peng L; Department of Respiratory Disease, Zhejiang Provincial People's Hospital, Hangzhou, China.
  • Yu Y; Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China.
  • Tai S; Department of Urology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China.
  • Qi H; Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Luo K; Biobank Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Kang X; Biobank Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Wang H; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Huang Y; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: huangyrrenji@163.com.
  • Zhang J; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: med-zhangjin@vip.sina.com.
  • Xue W; Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: uroxuewei@163.com.
Eur Urol ; 83(2): 163-172, 2023 02.
Article en En | MEDLINE | ID: mdl-35715365
ABSTRACT

BACKGROUND:

FH-deficient renal cell carcinoma (RCC) is a rare and exceptionally aggressive RCC subtype. There is currently limited understanding of the molecular alterations, pathogenesis, survival outcomes, and systemic therapy efficacy for this cancer.

OBJECTIVE:

To perform a retrospective multicenter analysis of molecular profiling and clinical outcomes for patients with FH-deficient RCC, with an emphasis on treatment response to first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI/TKI) versus bevacizumab plus erlotinib (Bev/Erlo) combination therapy in patients with advanced disease. DESIGN, SETTING, AND

PARTICIPANTS:

The study included 77 cases of FH-deficient RCC from 15 centers across China. OUTCOME MEASUREMENTS AND STATISTICAL

ANALYSIS:

Clinical characteristics, molecular correlates, 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging, and treatment outcomes were analyzed. RESULTS AND

LIMITATIONS:

A total of 77 patients were identified, including 70 cases with a germline FH alteration (hereditary leiomyomatosis RCC syndrome [HLRCC]-associated RCC) and seven patients with somatic FH loss. Recurrent pathogenic alterations were found in NF2 (six/57, 11%), CDH1 (six/57, 11%), PIK3CA (six/57, 11%), and TP53 (five/57, 8.8%). Sixty-seven patients were evaluable for response to first-line systemic therapy with Bev/Erlo (n = 12), TKI monotherapy (n = 29), or ICI/TKI (n = 26). ICI/TKI combination therapy was associated with more favorable overall survival on systemic treatment (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.90) and progression-free survival on first-line therapy (HR 0.22, 95% CI 0.07-0.71) compared to Bev/Erlo combination therapy. The main limitation is the retrospective study design.

CONCLUSIONS:

We described the genomic characteristics of FH-deficient RCC in an Asian population and observed a favorable response to ICI/TKI combinational therapy among patients with advanced disease. PATIENT

SUMMARY:

This real-world study provides evidence supporting the antitumour activity of combining molecular targeted therapy plus immunotherapy for kidney cancer deficient in fumarate hydratase. Further studies are needed to investigate the efficacy of this combination strategy in this rare cancer.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Uterinas / Carcinoma de Células Renales / Neoplasias Renales Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Eur Urol Año: 2023 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Uterinas / Carcinoma de Células Renales / Neoplasias Renales Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Eur Urol Año: 2023 Tipo del documento: Article País de afiliación: China