Abstract 1541P
Background
Introduction of tyrosine kinase inhibitors (TKIs) led to a greatly improved survival of advanced gastrointestinal stromal tumors (GIST). Imatinib was registered as first line palliative therapy in 2001 with a median progression free survival (mPFS) of 20.3 months. Furthermore, sunitinib and regorafenib have shown efficacy in the registration studies (mPFS of 5.6 months and 4.8 months resp.). Still, development of novel agents is needed to overcome TKI resistant GIST. The aim of this retrospective cohort study was to provide real-world response and survival data of approved TKIs to serve as reference point for new agents under development.
Methods
All patients diagnosed with GIST between 2009-2020, treated in 5 expertise centers in the Netherlands were registered in the Dutch GIST Registry and included. The objective response rate (ORR) for patients with advanced GIST treated with imatinib, sunitinib and regorafenib was calculated and subdivided by mutation subgroup. Furthermore, mPFS and overall survival (OS) were estimated using the Kaplan-Meier method.
Results
In total 1253 patients were included, 330 (26%) of them had advanced GIST at diagnosis. Overall, 419 patients were treated with TKIs in the palliative setting. The ORR for imatinib was 62% for all patients, 70% for KIT exon 11 mutated GIST, 40% for patients with a KIT exon 9 mutation and 48% for the group with other mutations. Patients benefited from imatinib with a mPFS of 34 months (95% confidence interval (CI): 29.8-38.2). Treatment with sunitinib and regorafenib resulted in mPFS of 11 months (95% CI: 8.9-13.1) and 7 months (95% CI: 4.3-9.8) respectively. The median OS for imatinib was 63 months (95% CI: 58.1-67.9), for sunitinib 21 months (95% CI: 15.5-26.5), and for regorafenib 13 months (95% CI: 10.9-15.1).
Conclusions
The response rate and survival outcomes of approved TKIs observed in this cohort demonstrate real-world data on treatment of advanced GIST. Compared to the registration studies, survival in real-life is significantly longer. Therefore, these results can serve as a new reference model for the future phase 3 therapeutic studies for advanced GIST, to compare and set targets for clinical benefit of novel agents.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Dutch GIST Registry was received from Deciphera, Novartis, Pfizer and Bayer.
Disclosure
R.H. Mathijssen: Financial Interests, Personal, Advisory Role, Consulting/advisory role: Servier; Financial Interests, Personal and Institutional, Other, patent: Pamgene (pending); Financial Interests, Institutional, Sponsor/Funding: Astellas; Financial Interests, Institutional, Sponsor/Funding: Bayer; Financial Interests, Institutional, Sponsor/Funding: Boehringer ingelheim; Financial Interests, Institutional, Sponsor/Funding: Cristal therapeutics; Financial Interests, Institutional, Sponsor/Funding: Pamgene; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Sponsor/Funding: Servier; Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Personal, Invited Speaker: Novartis. H. Gelderblom: Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Ipsen; Financial Interests, Institutional, Sponsor/Funding: Deciphera; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo. N. Steeghs: Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role: Ellipses Pharma.; Financial Interests, Institutional, Advisory Role: AIMM Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Astrazenica/medimmune; Financial Interests, Institutional, Sponsor/Funding: bayer; Financial Interests, Institutional, Sponsor/Funding: bristol-Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: GlaxoSmithKline; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Sponsor/Funding: Genentech/Roche; Financial Interests, Institutional, Sponsor/Funding: Blueprint Medicines; Financial Interests, Institutional, Sponsor/Funding: AB Science; Financial Interests, Institutional, Sponsor/Funding: Deciphera; Financial Interests, Institutional, Sponsor/Funding: Genentech; Financial Interests, Institutional, Sponsor/Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: Merus; Financial Interests, Institutional, Sponsor/Funding: Lilly; Financial Interests, Institutional, Sponsor/Funding: Incyte; Financial Interests, Institutional, Sponsor/Funding: Pierre Fabre; Financial Interests, Institutional, Sponsor/Funding: Abbvie; Financial Interests, Institutional, Sponsor/Funding: Actuate Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Cytovation; Financial Interests, Institutional, Sponsor/Funding: InteRNA; Financial Interests, Institutional, Sponsor/Funding: Array BioPharma; Financial Interests, Institutional, Sponsor/Funding: Cantargia AB; Financial Interests, Institutional, Sponsor/Funding: Taiho Pharmaceutical; Financial Interests, Institutional, Sponsor/Funding: Takeda. All other authors have declared no conflicts of interest.