Survival of Advanced/recurrent Gastrointestinal Stromal Tumors Treated with Tyrosine Kinase Inhibitors in Taiwan: a Nationwide Registry Study

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2024 Jul 11

PMID 38992597

Authors

Hui-Jen Tsai

Yan-Shen Shan

Ching-Yao Yang

Chin-Fu Hsiao

Chung-Hsin Tsai

Chuan-Cheng Wang

Ming-Tsan Lin

Chun-Fu Ting

De-Chuan Chan

Te-Hung Chen

Chueh-Chuan Yen

Yen-Yang Chen

Hsuan-Yu Lin

Ta-Sen Yeh

Ching-Liang Ho

Tze-Yu Shieh

Li-Yaun Bai

Jun-Te Hsu

I-Shu Chen

Li-Tzong Chen

Chun-Nan Yeh

Affiliations

Soon will be listed here.

Abstract

Background: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan.

Methods: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival.

Results: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89).

Conclusions: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

References

Heinrich M, Rankin C, Blanke C, Demetri G, Borden E, Ryan C . Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017; 3(7):944-952. PMC: 5727908. DOI: 10.1001/jamaoncol.2016.6728. View

Mohammadi M, IJzerman N, den Hollander D, Bleckman R, Oosten A, Desar I . Improved Efficacy of First-Line Imatinib in Advanced Gastrointestinal Stromal Tumors (GIST): The Dutch GIST Registry Data. Target Oncol. 2023; 18(3):415-423. PMC: 10191911. DOI: 10.1007/s11523-023-00960-y. View

Blay J, Serrano C, Heinrich M, Zalcberg J, Bauer S, Gelderblom H . Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020; 21(7):923-934. PMC: 8383051. DOI: 10.1016/S1470-2045(20)30168-6. View

Demetri G, van Oosterom A, Garrett C, Blackstein M, Shah M, Verweij J . Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006; 368(9544):1329-38. DOI: 10.1016/S0140-6736(06)69446-4. View

Heinrich M, Griffith D, Druker B, Wait C, Ott K, Zigler A . Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood. 2000; 96(3):925-32. View

Blanke C, Demetri G, von Mehren M, Heinrich M, Eisenberg B, Fletcher J . Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008; 26(4):620-5. DOI: 10.1200/JCO.2007.13.4403. View

Heinrich M, Owzar K, Corless C, Hollis D, Borden E, Fletcher C . Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest.... J Clin Oncol. 2008; 26(33):5360-7. PMC: 2651078. DOI: 10.1200/JCO.2008.17.4284. View

Blanke C, Rankin C, Demetri G, Ryan C, von Mehren M, Benjamin R . Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008; 26(4):626-32. DOI: 10.1200/JCO.2007.13.4452. View

Wozniak A, Rutkowski P, Schoffski P, Ray-Coquard I, Hostein I, Schildhaus H . Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a european multicenter analysis based on ConticaGIST. Clin Cancer Res. 2014; 20(23):6105-16. DOI: 10.1158/1078-0432.CCR-14-1677. View

10.

Joensuu H, Roberts P, Sarlomo-Rikala M, Andersson L, Tervahartiala P, Tuveson D . Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001; 344(14):1052-6. DOI: 10.1056/NEJM200104053441404. View

11.

Demetri G, von Mehren M, Blanke C, Van Den Abbeele A, Eisenberg B, Roberts P . Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002; 347(7):472-80. DOI: 10.1056/NEJMoa020461. View

12.

Hu C, Yeh C, Chen J, Tsai C, Wang S, Cheng C . Regorafenib treatment outcome for Taiwanese patients with metastatic gastrointestinal stromal tumors after failure of imatinib and sunitinib: A prospective, non-randomized, single-center study. Oncol Lett. 2020; 20(3):2131-2142. PMC: 7400021. DOI: 10.3892/ol.2020.11756. View

13.

Doi T, Kurokawa Y, Sawaki A, Komatsu Y, Ozaka M, Takahashi T . Efficacy and safety of TAS-116, an oral inhibitor of heat shock protein 90, in patients with metastatic or unresectable gastrointestinal stromal tumour refractory to imatinib, sunitinib and regorafenib: a phase II, single-arm trial. Eur J Cancer. 2019; 121:29-39. DOI: 10.1016/j.ejca.2019.08.009. View

14.

Rubio-Casadevall J, Borras J, Carmona-Garcia M, Ameijide A, Gonzalez-Vidal A, Ortiz M . Correlation between mutational status and survival and second cancer risk assessment in patients with gastrointestinal stromal tumors: a population-based study. World J Surg Oncol. 2015; 13:47. PMC: 4336765. DOI: 10.1186/s12957-015-0474-0. View

15.

Verschoor A, Bovee J, Overbeek L, Hogendoorn P, Gelderblom H . The incidence, mutational status, risk classification and referral pattern of gastro-intestinal stromal tumours in the Netherlands: a nationwide pathology registry (PALGA) study. Virchows Arch. 2018; 472(2):221-229. PMC: 5856869. DOI: 10.1007/s00428-017-2285-x. View

16.

Heinrich M, Maki R, Corless C, Antonescu C, Harlow A, Griffith D . Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol. 2008; 26(33):5352-9. PMC: 2651076. DOI: 10.1200/JCO.2007.15.7461. View

17.

Incorvaia L, Fanale D, Vincenzi B, De Luca I, Bartolotta T, Cannella R . Type and Gene Location of Mutations Predict Progression-Free Survival to First-Line Imatinib in Gastrointestinal Stromal Tumors: A Look into the Exon. Cancers (Basel). 2021; 13(5). PMC: 7956844. DOI: 10.3390/cancers13050993. View

18.

Kang Y, George S, Jones R, Rutkowski P, Shen L, Mir O . Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021; 39(28):3128-3139. PMC: 8478403. DOI: 10.1200/JCO.21.00217. View

19.

Rutkowski P, Nowecki Z, Debiec-Rychter M, Grzesiakowska U, Michej W, Wozniak A . Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). J Cancer Res Clin Oncol. 2007; 133(9):589-97. DOI: 10.1007/s00432-007-0202-4. View

20.

. Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol. 2010; 28(7):1247-53. PMC: 2834472. DOI: 10.1200/JCO.2009.24.2099. View