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Targeted Oncology
Published in: Targeted Oncology 3/2023

Open Access 20-04-2023 | Gastrointestinal Stromal Tumor | Original Research Article

Improved Efficacy of First-Line Imatinib in Advanced Gastrointestinal Stromal Tumors (GIST): The Dutch GIST Registry Data

Authors: Mahmoud Mohammadi, Nikki S. IJzerman, Dide den Hollander, Roos F. Bleckman, Astrid W. Oosten, Ingrid M. E. Desar, An K. L. Reyners, Neeltje Steeghs, Hans Gelderblom

Published in: Targeted Oncology | Issue 3/2023

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Abstract

Background

Patients with unresectable and metastasized gastrointestinal stromal tumor (GIST) experienced a remarkable improvement of progression-free survival (PFS) and overall survival (OS) after the introduction of imatinib. Our hypothesis is that the outcomes of treatment with imatinib are even better nowadays compared with the registration trials that were performed two decades ago. To study this, we used real-life data from a contemporary registry.

Methods

A multicenter, retrospective study was performed by exploring clinical data from a prospective real-life clinical database, the Dutch GIST Registry (DGR). Patients with advanced GIST treated with first-line imatinib were included and PFS (primary outcome) and OS (secondary outcome) were analyzed. Results of our study were compared with published results of the European Organisation for Research and Treatment of Cancer (EORTC) 62005 trial, which marked the first era of imatinib in the treatment of GIST.

Results

Overall, 420 of the 435 patients treated with imatinib in the DGR had recorded response evaluation and were included in the analysis. During a median follow-up of 35.0 months (range 2.0–136.0), progression of GIST was eventually observed in 217 patients (51.2%). The DGR cohort showed a longer median PFS (33.0 months, 95% confidence interval [CI] 28.4–37.6) compared with the EORTC 62005 trial (an estimated PFS of 19.5 months). Additionally, the median OS of 68.0 months (95% CI 56.1–80.0) was longer than the exposed median OS (46.8 months) published in the long-term follow-up results of the EORTC 62005 trial (median follow-up duration 10.9 years).

Conclusion

This study provides an update on outcomes of imatinib in the treatment of advanced GIST patients and demonstrates improved clinical outcomes since the first randomized studies of imatinib 2 decades ago. Furthermore, these results represent outcomes in real-world clinical practice and can serve as a reference when evaluating effectiveness of imatinib in patients with advanced GIST.
Literature
1.
Verschoor AJ, Bovee J, Overbeek LIH, Hogendoorn PCW, 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):221–9.CrossRefPubMedPubMedCentral
2.
Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in Western Sweden. Cancer. 2005;103(4):821–9.CrossRefPubMed
3.
Joensuu H, Vehtari A, Riihimaki J, Nishida T, Steigen SE, Brabec P, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265–74.CrossRefPubMed
4.
Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364(9440):1127–34.CrossRefPubMed
5.
Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, et al. 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.CrossRefPubMed
6.
Casali PG, Zalcberg J, Le Cesne A, Reichardt P, Blay JY, Lindner LH, et al. Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on imatinib at two dose levels. J Clin Oncol. 2017;35(15):1713–20.CrossRefPubMed
7.
Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, et al. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017;18(8):1089–103.CrossRefPubMedPubMedCentral
8.
Tap WD, Wagner AJ, Schoffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, et al. Effect of doxorubicin plus olaratumab vs doxorubicin plus placebo on survival in patients with advanced soft tissue sarcomas: the ANNOUNCE randomized clinical trial. JAMA. 2020;323(13):1266–76.CrossRefPubMedPubMedCentral
9.
Schwartz LH, Litiere S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-Update and clarification: from the RECIST committee. Eur J Cancer. 2016;62:132–7.CrossRefPubMedPubMedCentral
10.
Casali PG, Blay JY, Abecassis N, Bajpai J, Bauer S, Biagini R, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(1):20–33.CrossRefPubMed
11.
Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, et al. 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.CrossRefPubMed
12.
DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000;231(1):51–8.CrossRefPubMedPubMedCentral
13.
Van Glabbeke M, Verweij J, Casali PG, Le Cesne A, Hohenberger P, Ray-Coquard I, et al. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol. 2005;23(24):5795–804.CrossRefPubMed
14.
Bauer S, Rutkowski P, Hohenberger P, Miceli R, Fumagalli E, Siedlecki JA, et al. 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. 2014;40(4):412–9.CrossRefPubMed
15.
Heinrich MC, Jones RL, Gelderblom H, George S, Schöffski P, Mehren MV, et al. INTRIGUE: a phase III, randomized, open-label study to evaluate the efficacy and safety of ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib. J Clin Oncol. 2022;40(36 Suppl): 359881.CrossRef
16.
Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. 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.CrossRefPubMed
17.
Kang Y-K, George S, Jones RL, Rutkowski P, Shen L, Mir O, et al. 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):3128–39.CrossRefPubMedPubMedCentral
18.
Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, 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. Lancet. 2013;381(9863):295–302.CrossRefPubMed
Metadata
Title
Improved Efficacy of First-Line Imatinib in Advanced Gastrointestinal Stromal Tumors (GIST): The Dutch GIST Registry Data
Authors
Mahmoud Mohammadi
Nikki S. IJzerman
Dide den Hollander
Roos F. Bleckman
Astrid W. Oosten
Ingrid M. E. Desar
An K. L. Reyners
Neeltje Steeghs
Hans Gelderblom
Publication date
20-04-2023
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 3/2023
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-023-00960-y

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