Journal of Surgery Concepts & Practice ›› 2025, Vol. 30 ›› Issue (05): 456-460.doi: 10.16139/j.1007-9610.2025.05.13
• Review • Previous Articles
TANG Haixiao, ZHANG Yun, HAN Gang, GONG Hangjun
Received:2024-12-26
Online:2025-09-25
Published:2025-12-09
CLC Number:
TANG Haixiao, ZHANG Yun, HAN Gang, GONG Hangjun. Progression in treatment of advanced gastrointestinal stromal tumors[J]. Journal of Surgery Concepts & Practice, 2025, 30(05): 456-460.
Tab 1
Efficacy of representative TKIs in advanced GISTs
| Treatment drug | KIT/platelet derived growth factor alpha mutated gastrointestinal stromal tumors | Platelet derived growth factor alpha D842V mutated gastrointestinal stromal tumors | |||
|---|---|---|---|---|---|
| First-line: Imatinib[ | Second-line: Sunitinib[ | Third-line: Regorafenib[ | Fourth-line: Avapritinib[ | Any: Avapritinib[ | |
| Objective response rate (%) | 68.1 | 17.6 | 7.2 | 9.4 | 91.0 |
| Stable disease rate(%) | 15.6 | Not available | 67.8 | 47.0 | 9.0 |
| Median progression-free survival (months) | 24.0 | 8.3 | 5.6 | 6.3 | 34.0 |
| [1] |
KELLY C M, GUTIERREZ SAINZ L, CHI P. The management of metastatic GIST: current standard and investigational therapeutics[J]. J Hematol Oncol, 2021, 14(1):2.
doi: 10.1186/s13045-020-01026-6 |
| [2] |
NAITO Y, NISHIDA T, DOI T. Current status of and future prospects for the treatment of unresectable or metastatic gastrointestinal stromal tumours[J]. Gastric Cancer, 2023, 26(3):339-351.
doi: 10.1007/s10120-023-01381-6 pmid: 36913072 |
| [3] |
KHOSROYANI H M, KLUG L R, HEINRICH M C. TKI treatment sequencing in advanced gastrointestinal stromal tumors[J]. Drugs, 2023, 83(1):55-73.
doi: 10.1007/s40265-022-01820-1 pmid: 36607590 |
| [4] |
HUANG W K, WU C E, WANG S Y, et al. Systemic therapy for gastrointestinal stromal tumor: current standards and emerging challenges[J]. Curr Treat Options Oncol, 2022, 23(9):1303-1319.
doi: 10.1007/s11864-022-00996-8 |
| [5] |
MECHAHOUGUI H, MICHAEL M, FRIEDLAENDER A. Precision oncology in gastrointestinal stromal tumors[J]. Curr Oncol, 2023, 30(5):4648-4662.
doi: 10.3390/curroncol30050351 pmid: 37232809 |
| [6] |
MANTESE G. Gastrointestinal stromal tumor: epidemio-logy, diagnosis, and treatment[J]. Curr Opin Gastroenterol, 2019, 35(6):555-559.
doi: 10.1097/MOG.0000000000000584 URL |
| [7] | SERRANO C, MARTÍN-BROTO J, ASENCIO-PASCUAL J M, et al. 2023 GEIS Guidelines for gastrointestinal stromal tumors[J]. Ther Adv Med Oncol, 2023,15: 17588359231192388. |
| [8] |
SHARMA A K, KIM T S, BAUER S, et al. Gastrointestinal stromal tumor: new insights for a multimodal approach[J]. Surg Oncol Clin N Am, 2022, 31(3):431-446.
doi: 10.1016/j.soc.2022.03.007 pmid: 35715143 |
| [9] | PANTALEO M A, URBINI M, SCHIPANI A, et al. SDHA germline variants in adult patients with SDHA-mutant gastrointestinal stromal tumor[J]. Front Oncol, 2022,11:778461. |
| [10] |
NAGANO H, OHYAMA S, SATO A, et al. Jejunal gastrointestinal stromal tumor that developed in a patient with neurofibromatosis type 1: a case report[J]. Diagn Pathol, 2023, 18(1):110.
doi: 10.1186/s13000-023-01398-6 pmid: 37789344 |
| [11] |
INOUE A, OTA S, YAMASAKI M, et al. Gastrointestinal stromal tumors: a comprehensive radiological review[J]. Jpn J Radiol, 2022, 40(11):1105-1120.
doi: 10.1007/s11604-022-01305-x pmid: 35809209 |
| [12] |
UNK M, JEZERŠEK NOVAKOVIĆ B, NOVAKOVIĆ S. Molecular mechanisms of gastrointestinal stromal tumors and their impact on systemic therapy decision[J]. Cancers (Basel), 2023, 15(5):1498.
doi: 10.3390/cancers15051498 URL |
| [13] |
STRAUSS G, GEORGE S. Gastrointestinal stromal tumors[J]. Curr Oncol Rep, 2025, 27(3):312-321.
doi: 10.1007/s11912-025-01636-8 pmid: 39985704 |
| [14] |
NAPOLITANO A, THWAY K, SMITH M J, et al. KIT exon 9-mutated gastrointestinal sstromal tumours: biology and treatment[J]. Chemotherapy, 2022, 67(2):81-90.
doi: 10.1159/000521751 URL |
| [15] |
WOZNIAK A, RUTKOWSKI P, SCHÖFFSKI P, et al. Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a European multicenter analysis based on ConticaGIST[J]. Clin Cancer Res, 2014, 20(23):6105-6116.
doi: 10.1158/1078-0432.CCR-14-1677 pmid: 25294914 |
| [16] |
MOHAMMADI M, GELDERBLOM H. Systemic therapy of advanced/metastatic gastrointestinal stromal tumors: an update on progress beyond imatinib, sunitinib, and regorafenib[J]. Expert Opin Investig Drugs, 2021, 30(2):143-152.
doi: 10.1080/13543784.2021.1857363 URL |
| [17] |
MOHAMMADI M, IJZERMAN N S, HOLLANDER D D, et al. Improved efficacy of first-line imatinib in advanced gastrointestinal stromal tumors (GIST): the Dutch gist registry data[J]. Target Oncol, 2023, 18(3):415-423.
doi: 10.1007/s11523-023-00960-y pmid: 37079223 |
| [18] |
CASALI P G, ABECASSIS N, ARO H T, et al. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2018, 29(Suppl 4):iv267.
doi: 10.1093/annonc/mdy320 URL |
| [19] |
CHI P, QIN L X, CAMACHO N, et al. Phase Ⅰb trial of the combination of imatinib and binimetinib in patients with advanced gastrointestinal stromal tumors[J]. Clin Cancer Res, 2022, 28(8):1507-1517.
doi: 10.1158/1078-0432.CCR-21-3909 URL |
| [20] |
CHI P, QIN L X, NGUYEN B, et al. Phase Ⅱ trial of imatinib plus binimetinib in patients with treatment-naive advanced gastrointestinal stromal tumor[J]. J Clin Oncol, 2022, 40(9):997-1008.
doi: 10.1200/JCO.21.02029 URL |
| [21] |
VERSCHUUR A C, BAJČIOVÁ V, MASCARENHAS L, et al. Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase Ⅰ/Ⅱ trial[J]. Cancer Chemother Pharmacol, 2019, 84(1):41-50.
doi: 10.1007/s00280-019-03814-5 |
| [22] | REICHARDT P, DEMETRI G D, GELDERBLOM H, et al. Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial[J]. BMC Cancer, 2016,16:22. |
| [23] |
SHEN G, ZHENG F, REN D, et al. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical deve-lopment[J]. J Hematol Oncol, 2018, 11(1):120.
doi: 10.1186/s13045-018-0664-7 |
| [24] | ZHOU Y, ZENG C, SUN X, et al. Activity of anlotinib in the second-line therapy of metastatic gastrointestinal stromal tumors: a prospective, multicenter, in vitro study[J]. Oncologist, 2023, 28(4):e191-e197. |
| [25] | BRČIĆ I, ARGYROPOULOS A, LIEGL-ATZWANGER B. Update on molecular genetics of gastrointestinal stromal tumors[J]. Diagnostics (Basel), 2021, 11(2):194. |
| [26] |
MARTIN-BROTO J, VALVERDE C, HINDI N, et al. REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase Ⅱ trial[J]. Mol Cancer, 2023, 22(1):127.
doi: 10.1186/s12943-023-01832-9 |
| [27] |
YEH C N, CHEN M H, CHEN Y Y, et al. A phase Ⅱ trial of regorafenib in patients with metastatic and/or a unresectable gastrointestinal stromal tumor harboring secondary mutations of exon 17[J]. Oncotarget, 2017, 8(27):44121-44130.
doi: 10.18632/oncotarget.v8i27 URL |
| [28] |
BAUER S, JONES R L, BLAY J Y, et al. Ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor after treatment with imatinib (INTRIGUE): a randomized, open-label, phase Ⅲ trial[J]. J Clin Oncol, 2022, 40(34):3918-3928.
doi: 10.1200/JCO.22.00294 URL |
| [29] |
LI J, CAI S, ZHOU Y, et al. Efficacy and safety of ripretinib in Chinese patients with advanced gastrointestinal stromal tumors as a fourth- or later-line therapy: a multicenter, single-arm, open-label phase Ⅱ study[J]. Clin Cancer Res, 2022, 28(16):3425-3432.
doi: 10.1158/1078-0432.CCR-22-0196 URL |
| [30] | JONES R L, SERRANO C, VON MEHREN M, et al. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: long-term efficacy and safety data from the NAVIGATOR phase Ⅰ trial[J]. Eur J Cancer, 2021,145:132-142. |
| [31] | JOSEPH C P, ABARICIA S N, ANGELIS M A, et al. Optimal avapritinib treatment strategies for patients with metastatic or unresectable gastrointestinal stromal tumors[J]. Oncologist, 2021, 26(4):e622-e631. |
| [32] | LI J, ZHANG X, DENG Y, et al. Efficacy and safety of avapritinib in treating unresectable or metastatic gastrointestinal stromal tumors: a phase Ⅰ/Ⅱ, open-label, multicenter study[J]. Oncologist, 2023, 28(2):187-e114. |
| [33] |
SERRANO C, BAUER S, GÓMEZ-PEREGRINA D, et al. Circulating tumor DNA analysis of the phase Ⅲ VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib[J]. Ann Oncol, 2023, 34(7):615-625.
doi: 10.1016/j.annonc.2023.04.006 URL |
| [34] |
DEMETRI G D, VON MEHREN M, BLANKE C D, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors[J]. N Engl J Med, 2002, 347(7):472-480.
doi: 10.1056/NEJMoa020461 URL |
| [35] |
HEINRICH M C, MAKI R G, CORLESS C L, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor[J]. J Clin Oncol, 2008, 26(33):5352-5359.
doi: 10.1200/JCO.2007.15.7461 pmid: 18955458 |
| [36] |
DEMETRI G D, REICHARDT P, KANG Y K, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial[J]. Lancet, 2013, 381(9863):295-302.
doi: 10.1016/S0140-6736(12)61857-1 pmid: 23177515 |
| [37] |
KANG Y K, GEORGE S, JONES R L, et al. Avapritinib versus regorafenib in locally advanced unresectable or metastatic GI stromal tumor: a randomized, open-label phase Ⅲ study[J]. J Clin Oncol, 2021, 39(28):3128-3139.
doi: 10.1200/JCO.21.00217 URL |
| [38] |
HEINRICH M C, JONES R L, VON MEHREN M, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial[J]. Lancet Oncol, 2020, 21(7):935-946.
doi: S1470-2045(20)30269-2 pmid: 32615108 |
| [1] | ZHANG Tianqi, LIU Yang, WEI Yunwei. Advances in the study of intestinal microecology in the development of hepatocellular carcinoma and its implications for clinical diagnosis and treatment [J]. Journal of Surgery Concepts & Practice, 2025, 30(05): 450-455. |
| [2] | XU Wanqian, ZHOU Chunhua, ZOU Duowu. Application and advancements of endoscopy in the management of pancreatic intraductal papillary mucinous neoplasm [J]. Journal of Surgery Concepts & Practice, 2025, 30(05): 369-377. |
| [3] | WANG Jun, WANG Lubing, HU Gangfeng, ZHANG Bo, HUANG Xia, HUANG Lei. Expression and clinical significance of KIF15, EGFR, and HER2 in gallbladder cancer [J]. Journal of Surgery Concepts & Practice, 2025, 30(05): 409-416. |
| [4] | WANG Yu, HU Kaixin, ZHAO Fengqing, LI Huangbao. Efficacy variations of adjuvant chemotherapy across disease stages in duodenal adenocarcinoma: a multivariate survival analysis based on the SEER database [J]. Journal of Surgery Concepts & Practice, 2025, 30(05): 428-437. |
| [5] | JI Bei, SHANG Zhengye, TUO Biguang, LIU Xuemei. Comprehensive diagnosis and treatment strategy for functional pancreas neuroendocrine neoplasm: a report of 3 cases [J]. Journal of Surgery Concepts & Practice, 2025, 30(05): 438-443. |
| [6] | HUANG Wenxin, HE Qining, Qi Debin, Cao Zichao, JIANG Yanzhi, WANG Pusen, QUE Weitao, ZHONG Lin. Assessment of indocyanine green fluorescence imaging in hepatectomy for primary liver carcinoma: short-term prognostic analysis [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 325-331. |
| [7] | TANG Zhenqi, LI Qi, LIU Hengchao, ZHANG Dong, GENG Zhimin. Construction and validation of a machine learning-based prediction model for very early recurrence after curative-intent resection for gallbladder cancer [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 316-324. |
| [8] | YUAN Xiaobing, ZHU Jianwei. Impact of miR-4674 expression changes on the biological characteristics of BGC-823 gastric cancer cell line [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 295-301. |
| [9] | CHEN Jiaqian, LIU Hongzhi, MENG Lingtian, ZHOU Weiping, CHENG Zhangjun, LOU Jianying, ZHENG Shuguo, BI Xinyu, WANG Jianming, GUO Wei, LI Fuyu, WANG Jian, ZHENG Yamin, LI Jingdong, CHENG Shi, HUANG Yao, ZENG Yongyi. Intrahepatic cholangiocarcinoma tumor size classification based on prognostic analysis: a retrospective multicenter study [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 332-338. |
| [10] | LI Yaqi, MO Shaobo, PENG Junjie. Progression in circulating tumor DNA detection for minimal residual disease in patients with colorectal cancer liver metastasis [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 351-357. |
| [11] | ZHI Yihao, ZHAO Xuan, ZHENG Minhua. Evolution and hot topics of laparoscopic sphincter-preserving surgery for low rectal cancer [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 358-363. |
| [12] | YANG Yue, ZHAO Lei. Advances in the concomitant chronic liver disease and colorectal cancer liver metastasis [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 364-368. |
| [13] | ZHU Zhenggang, Joji Kitayama, Hyung-Ho Kim, Jimmy Bok-Yan So, CAO Hui, CHEN Lin, CHENG Xiangdong, HU Jiankun, Motohiro Imano, Hironori Ishigami, Ye Seob Jee, Jong-Han Kim, Yasuhiro Kodera, LIANG Han, LIU Xiaowen, LU Sheng, MOU Yiping, NIE Mingming, Won Jun Seo, WANG Yanong, WU Dan, XU Zekuan, Hironori Yamaguchi, YAN Chao, YANG Zhongyin, YIN Kai, Yutaka Yonemura, Wei-Peng Yong, YU Jiren, ZHANG Jun, Asian Gastric Cancer NIPS Treatment Collaborative Group, Shanghai Anticancer Association, Committee of Peritoneal Tumor. Asian consensus on normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis [J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 277-294. |
| [14] | WU Chunxiao, PANG Yi, CHEN Lei, SHI Yan, GU Kai. Incidence and mortality analysis of biliary tract cancer in Shanghai: population-based study from 2002 to 2020 [J]. Journal of Surgery Concepts & Practice, 2025, 30(03): 214-222. |
| [15] | JIN Jiabin, MA Junjun, YE Feng, MA Shiyu, CHEN Jingxian. Investigation of the mechanism of Huaier (Vanderbylia robiniophila) anti-pancreatic cancer based on network pharmacology, molecular docking, and two-sample Mendelian randomization analysis [J]. Journal of Surgery Concepts & Practice, 2025, 30(03): 247-255. |
| Viewed | ||||||
|
Full text |
|
|||||
|
Abstract |
|
|||||