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

作者：Michael C. Heinrich, Xinhua Zhang, Robin L. Jones, Suzanne George, César Serrano, Yanhong Deng, Sebastian Bauer, Shirong Cai, Xin Wu, Yongjian Zhou, Kaixiong Tao, Zhichao Zheng, Jun Zhang, Yuehong Cui, Hui Cao, Meining Wang, Jin Hu, Jason Yang, Jian Li, Lin Shen · 发表于：Clinical Cancer Research · 年份：2023 · DOI：10.1158/1078-0432.ccr-23-1861 · 被引用次数：9 · 研究领域：Gastrointestinal Tumor Research and Treatment、Gastrointestinal Bleeding Diagnosis and Treatment、Sarcoma Diagnosis and Treatment

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; ALposABPneg), and other KIT mutations (OTHERS). RESULTS: Sixty KIT ALposABPneg and 100 KIT OTHERS predominantly heavily pretreated patients (61.3% with ≥3 prior TKIs) were included. ORR was significantly higher in KIT ALposABPneg 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 ALposABPneg 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 ...