Clinical Benefit of Avapritinib in <i>KIT-</i>Mutant Gastrointestinal Stromal Tumors: A <i>Post Hoc</i> Analysis of the Phase I NAVIGATOR and Phase I/II CS3007-001 Studies

作者全名："Heinrich, Michael C.; Zhang, Xinhua; Jones, Robin L.; George, Suzanne; Serrano, Cesar; Deng, Yanhong; Bauer, Sebastian; Cai, Shirong; Wu, Xin; Zhou, Yongjian; Tao, Kaixiong; Zheng, Zhichao; Zhang, Jun; Cui, Yuehong; Cao, Hui; Wang, Meining; Hu, Jin; Yang, Jason; Li, Jian; Shen, Lin"

作者地址："[Heinrich, Michael C.] Portland VA Hlth Care Syst, Portland, OR USA; [Zhang, Xinhua] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Gastrointestinal Surg, Guangzhou, Peoples R China; [Jones, Robin L.] Royal Marsden Hosp, London, England; [Jones, Robin L.] Inst Canc Res, London, England; [George, Suzanne] Dana Farber Canc Inst, Sarcoma Canc Ctr, Boston, MA USA; [Serrano, Cesar] Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain; [Deng, Yanhong] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Med Oncol, Guangzhou, Peoples R China; [Bauer, Sebastian] West German Canc Ctr, Dept Med Oncol, Essen, Germany; [Cai, Shirong] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou, Peoples R China; [Wu, Xin] Chinese Peoples Liberat Army Gen Hosp, Dept Gen Surg, Beijing, Peoples R China; [Zhou, Yongjian] Fujian Med Univ Union Hosp, Dept Gastroenterol, Fuzhou, Fujian, Peoples R China; [Tao, Kaixiong] Huazhong Univ Sci & Technol, Wuhan Union Hosp, Tongji Med Coll, Dept Gastroenterol, Wuhan, Peoples R China; [Zheng, Zhichao] Liaoning Canc Hosp & Inst, Dept Gastrosurg, Shenyang, Liaoning, Peoples R China; [Zhang, Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Chongqing, Peoples R China; [Cui, Yuehong] Fudan Univ, Zhongshan Hosp, Dept Med Oncol, Shanghai, Peoples R China; [Cao, Hui] Shanghai Jiao Tong Univ, Renji Hosp, Dept Gastroenterol, Sch Med, Shanghai, Peoples R China; [Wang, Meining] CStone Pharmaceut Suzhou, Med Affairs, Suzhou, Peoples R China; [Hu, Jin; Yang, Jason] CStone Pharmaceut Suzhou, Clin Dept, Suzhou, Peoples R China; [Li, Jian; Shen, Lin] Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Dept Gastrointestinal Oncol,Lab Carcinogenesis & T, Beijing, Peoples R China; [Li, Jian; Shen, Lin] Peking Univ, Beijing Canc Hosp & Inst, Dept Gastrointestinal Oncol, Lab Carcinogenesis & Translat Res,Minist Educ,Sch, 52 Fucheng Rd, Beijing 100142, Peoples R China"

通信作者："Li, J; Shen, L (通讯作者)，Peking Univ, Beijing Canc Hosp & Inst, Dept Gastrointestinal Oncol, Lab Carcinogenesis & Translat Res,Minist Educ,Sch, 52 Fucheng Rd, Beijing 100142, Peoples R China."

来源：CLINICAL CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001163758000025

JCR分区：Q1

影响因子：10

年份：2024

卷号：30

期号：4

开始页：719

结束页：728

文献类型：Article

关键词：　

摘要："Purpose: The efficacy of the selective KIT/PDGFRA inhibitor avapritinib (300 mg once daily) was explored in patients with non-PDGFRA-mutant gastrointestinal stromal tumors (GISTs) from the phase I NAVIGATOR and phase I/II CS3007-001 trials. Patients and Methods: Adults with unresectable/metastatic, KIT-only-mutant GISTs and progression following >= 1 tyrosine kinase inhibitors (TKIs) were included in this post hoc analysis. Baseline mutational status was identified in tumor and plasma. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent radiology review per modified RECIST v1.1 in patients harboring KIT activation-loop mutations (KIT exons 17 or 18) without ATP binding-pocket mutations (KIT exons 13 or 14; AL(pos)ABP(neg)), and other KIT mutations (OTHERS). Results: Sixty KIT AL(pos)ABP(neg) and 100 KIT OTHERS predominantly heavily pretreated patients (61.3% with >= 3 prior TKIs) were included. ORR was significantly higher in KIT AL(pos)ABP(neg) than KIT OTHERS patients (unadjusted: 26.7% vs. 12.0%; P = 0.0852; adjusted: 31.4% vs. 12.1%; P = 0.0047). Median PFS (mPFS) was significantly longer in KIT AL(pos)ABP(neg) patients compared with KIT OTHERS patients (unadjusted: 9.1 vs. 3.5 months; P = 0.0002; adjusted: 9.1 vs. 3.4 months; P < 0.0001), and longer in second- versus later-line settings (19.3 vs. 5.6-10.6 months). Benefit with avapritinib was observed in patients with KIT exon 9 mutations in the >= 4 line settings (mPFS: 5.6 and 3.7 months for 4 line and >4 line, respectively). Conclusions: Avapritinib showed greater antitumor activity in patients with GISTs harboring KIT AL(pos)ABP(neg) mutations versus KIT OTHERS, and may be considered in the former subpopulation. Patients with KIT exon 9 mutations may also benefit in >= 4 line settings."

基金机构："n/a; CStone Pharmaceuticals (Suzhou); Jiangsu, China"

基金资助正文："This study was funded by CStone Pharmaceuticals (Suzhou), Jiangsu, China. We thank all study participants and their families, and the investigators and study teams at each study site. We also thank Jacqueline Kolston PhD (Parexel International) for providing medical writing support under the direction of the authors, which was funded by CStone Pharmaceuticals (Suzhou) in accordance with Good Publications Practice (GPP4) guidelines."