"Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study"

作者全名："Li, Jian; Zhang, Xinhua; Deng, Yanhong; Wu, Xin; Zheng, Zhichao; Zhou, Yongjian; Cai, Shirong; Zhang, Yanqiao; Zhang, Jun; Tao, Kaixiong; Cui, Yuehong; Cao, Hui; Shen, Kuntang; Yu, Jiren; Zhou, Ye; Ren, Wenxiao; Qu, Chenglin; Zhao, Wanqi; Hu, Jin; Wang, Wei; Yang, Jason; Shen, Lin"

作者地址："[Li, Jian; Shen, Lin] Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Dept Gastrointestinal Oncol,Lab Carcinogenesis & T, 2 Fucheng Rd, Beijing 100142, Peoples R China; [Zhang, Xinhua; Cai, Shirong] Sun Yat sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou, Peoples R China; [Deng, Yanhong] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Med Oncol, Guangzhou, Peoples R China; [Wu, Xin] Chinese Peoples Liberat Army Gen Hosp, Dept Gen Surg, Beijing, Peoples R China; [Zheng, Zhichao] Liaoning Canc Hosp & Inst, Dept Gastrosurg, Shenyang, Peoples R China; [Zhou, Yongjian] Fujian Med Univ, Dept Gastroenterol, Union Hosp, Fuzhou, Peoples R China; [Zhang, Yanqiao] Harbin Med Univ Canc Hosp, Dept Gastrointestinal Med Oncol, Harbin, Peoples R China; [Zhang, Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Chongqing, Peoples R China; [Tao, Kaixiong] Huazhong Univ Sci & Technol, Wuhan Union Hosp, Tongji Med Coll, Dept Gastroenterol, Wuhan, Peoples R China; [Cui, Yuehong] Fudan Univ, Dept Med Oncol, Zhongshan Hosp, Shanghai, Peoples R China; [Cao, Hui] Shanghai Jiao Tong Univ, Dept Gastroenterol, Renji Hosp, Sch Med, Shanghai, Peoples R China; [Shen, Kuntang] Fudan Univ, Dept Gen Surg, Zhongshan Hosp, Shanghai, Peoples R China; [Yu, Jiren] Zhejiang Univ, Affiliated Hosp 1, Dept Gastroenterol, Hangzhou, Peoples R China; [Zhou, Ye] Fudan Univ, Dept Gastr Surg, Shanghai Canc Ctr, Shanghai, Peoples R China; [Ren, Wenxiao; Qu, Chenglin; Zhao, Wanqi; Hu, Jin; Wang, Wei; Yang, Jason] CStone Pharmaceut Suzhou, Suzhou, Peoples R China"

通信作者："Shen, L (通讯作者)，Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Dept Gastrointestinal Oncol,Lab Carcinogenesis & T, 2 Fucheng Rd, Beijing 100142, Peoples R China."

来源：ONCOLOGIST

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000893584400001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：tyrosine kinase inhibitor; avapritinib; gastrointestinal stromal tumors; PDGFRA D842V; fourth-line therapy

摘要："Background Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST). Methods Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR). Results No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade >= 3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both. Overall survival data were immature and not calculated. Conclusion Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939). This article evaluates the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors."

基金机构："CStone Pharmaceuticals, Suzhou, China; Blueprint Medicines Corporation"

基金资助正文："CStone Pharmaceuticals, Suzhou, China & Blueprint Medicines Corporation"