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. 2024 Nov 9;150(11):489.
doi: 10.1007/s00432-024-05965-2.

Overall survival of patients with KIT-mutant metastatic GIST in the era of multiple kinase inhibitor availability

Valerie Haller  1   2 , Carina Reiff  1   2 , Rainer Hamacher  1   2 , Karina Kostbade  1   2 , Moritz Kaths  2   3 , Juergen Treckmann  2   3 , Stefanie Bertram  2   4 , Yasmin Zaun  1   2 , Sebastian Bauer  5   6 , Johanna Falkenhorst  1   2
Affiliations

Overall survival of patients with KIT-mutant metastatic GIST in the era of multiple kinase inhibitor availability

Valerie Haller et al. J Cancer Res Clin Oncol. .

Erratum in

Abstract

Purpose: The prognosis of patients with metastatic GIST and imatinib-sensitive primary mutations has significantly improved. However, limited data are available to inform patients about outcomes across different lines of treatment. This retrospective analysis aims to evaluate patient outcomes at a large German GIST referral center over the past 15 years.

Patients and methods: Overall survival (OS) and progression-free survival (PFS) were analyzed in patients with metastatic GIST, with diagnosis of metastases between 2008 and 2021, when at least three lines of treatment were available in Germany (n = 174).

Results: The median overall survival far exceeds historical data for patients with primary exon 11 and exon 9 mutations (median OS in palliative treatment with imatinib: 7.1 years; median OS in second-line palliative treatment with sunitinib: 2.9 years; median OS in third-line palliative treatment with regorafenib: 1.9 years). Among those patients who received palliative imatinib treatment, no significant difference in median OS survival was observed between those who had received perioperative imatinib for localized disease and those who did not. Furthermore, the location of metastases significantly impacted survival, whereas the time between the initial diagnosis and the diagnosis of metastases had no significant effect on survival.

Conclusion: In conclusion, this study provides a novel, real-world reference for survival outcomes in patients with metastatic GIST.

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Conflict of interest statement

Johanna Falkenhorst: Consulting or Advisory role: Deciphera Pharmaceuticals, DIGIMED Verlag GmbH Sebastian Bauer: Honoraria: Novartis, Pharmamar, GlaxoSmithKline, Deciphera Consulting or Advisory Role: Blueprint Medicines, Bayer, Lilly, Deciphera, Nanobiotix, Daiichi Sankyo, Exelixis, Janssen-Cilag, ADC Therapeutics, Mundipharma, GlaxoSmithKline, Adcendo, Boehringer Ingelheim, IDRX Research Funding: Blueprint Medicines, Novartis, Incyte (Inst) Travel, Accommodations, Expenses: Pharmamar.

Figures

Fig. 1
Fig. 1
CONSORT diagram. The institutional database comprised a total of n = 771 patients. Among these, 377 patients with localized disease were excluded from the analysis. Additionally, 158 patients whose diagnosis of metastatic disease predated 2008 were also excluded. Furthermore, 62 patients lacked an imatinib-sensitive mutation, resulting in a final cohort size of n = 174 patients. Among these, n = 138 harbored primary KIT exon 11 mutations, while n = 36 exhibited primary KIT exon 9 mutations
Fig. 2
Fig. 2
Kaplan-Meier estimation for overall survival A and B): Calculated from the first treatment with imatinib (IM) for metastatic GIST until last follow-up (FU) or death (2A) and comparison of two cohorts: Primary KIT exon 9 or KIT exon 11 mutation (2B). C and D): Kaplan-Meier estimation from the first treatment with sunitinib (SU) (2C) and comparison of two cohorts (2D). E and F): Kaplan-Meier estimation from the first treatment with regorafenib (REGO) (2E) also divided into two cohorts (2F). G): Median overall survival in years based on palliative treatment lines in primary exon 11 and exon 9 mutant GIST, with confidence intervals (2G)
Fig. 3
Fig. 3
A and B): Overall survival curve calculated from first treatment with imatinib until last FU or death, based on time to metastases. (3A). Overall survival curve calculated from the first treatment with imatinib until last follow-up (FU) or death, based on the location of metastases (3B). C and D): Overall survival curve calculated from the first treatment with imatinib until last FU or death, based on prior perioperative imatinib treatment (3C). Time to progression curve calculated from the date of first imatinib for metastatic disease until progression, based on prior perioperative imatinib treatment (3D)
Fig. 4
Fig. 4
A and B: Survival analyses calculated from first treatment with imatinib for metastatic GIST to last follow-up (FU) or death within our cohort compared with long-term results of imatinib in advanced GIST, analysis of the phase 3 SWOG Intergroup Trial S0033, excluding wild-type mutations for better comparability (Heinrich et al. 2017)
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References

    1. Bauer S et al (2014) Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib – analysis of prognostic factors (EORTC-STBSG collaborative study). Eur J Surg Oncol (EJSO) 40:412–419 - PubMed
    1. Bauer S, Jones RL, Blay JY, Gelderblom H, George S, Schoffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Su Y, Meade J, Wang T, Sherman ML, Ruiz-Soto R and M. C. Heinrich. 2022. ‘Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial’. J Clin Oncol, 40: 3918–3928 - PMC - PubMed
    1. Ben-Ami E, Barysauskas CM, von Mehren M, Heinrich MC, Corless CL, Butrynski JE, Morgan JA, Wagner AJ, Choy E, Yap JT, Van den Abbeele AD, Solomon SM, Fletcher JA, Demetri GD, George S (2016) Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. Ann Oncol 27:1794–1799 - PMC - PubMed
    1. Blanke CD, Demetri GD, Von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, Corless CL, Fletcher CD, Roberts PJ, Heinz D, Wehre E, Nikolova Z, Joensuu H (2008) 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 26:620–625 - PubMed
    1. Blay J-Y et al (2017) ‘Improved survival using specialized multidisciplinary board in sarcoma patients’. Ann Oncol - PMC - PubMed

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