Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China

作者：Li, Jian; Zhang, Jun; Zhang, Yanqiao; Qiu, Haibo; Zhou, Yanbing; Zhou, Yongjian; Zhang, Xinhua; Zhou, Ye; Zhu, Yuping; Li, Yong; Wang, Ming; Shen, Kuntang; Tao, Kaixiong; Wu, Xin; Wang, Haijiang; Zhang, Bo; Ling, Jiayu; Ye, Yingjiang; Wu, Xingye; Qu, Hongyan; Ma, Yue; Jiao, Xuelong; Zheng, Hualong; Jin, Jiejie; Liu, Zhuo; Tan, Ming; Fang, Yong; Zhang, Peng; Zhang, Nan; Lei, Cheng; Cai, Zhaolun; Liang, Bin; Peng, Zhangyan; Huang, Zhao; Dong, Juan; Shen, Lin^*

来源：European Journal of Cancer, 2024, 196: 113439.

DOI：10.1016/j.ejca.2023.113439

• Ripretinib
• Sunitinib
• Second -line treatment
• Gastrointestinal stromal tumor

Aim: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second -line treatment in Chinese GIST patients. Methods: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). Results: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had pri-mary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0.99, 95 % CI 0.57, 1.69; nominal p = 0.92; median PFS [mPFS] 10.3 vs 8.3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0.46, 95 % CI 0.23, 0.92; nominal p = 0.03; mPFS not reached in ripretinib arm and 4 & sdot;9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). Conclusions: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second -line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.

• 单位
  1; 复旦大学; 哈尔滨医科大学; 四川大学; 6; 河北医科大学; 华中科技大学; 中国科学院研究生院; 青岛大学; 北京大学; 上海交通大学; 中山大学