Abstract 1513P
Background
GISTs are driven by genetic aberrations, mostly observed within KIT and PDGFRA genes. Standard first-line therapy for inoperable/metastatic GIST includes imatinib. The presence of specific genetic alterations may impact imatinib efficacy and patients' survival. We aimed to analyze the impact of KIT and PDGFR mutation in patients with GIST treated in the first line with imatinib in two cohorts according to anatomical location.
Methods
Prospectively collected data of patients with advanced GIST with known mutational status (KIT/PDGFRA) and treated with imatinib between 01/2001 and 12/2021 were analyzed. Survival analyses were performed using the Kaplan-Meier method and log-rank test, while multivariate Cox regression was used to identify factors associated with progression-free survival (PFS) and overall survival (OS).
Results
344 patients (46.5% female, 35.8% with gastric GIST) have been included. Frequency of KIT and PDGFRA mutations are presented in the table. With the median follow-up was 5.2years, median PFS was 40.6 (95%CI 32.8-48.5) months, median OS 82.4 (95%CI 67.7-97.1) months. In multivariate analysis factors correlated with longer PFS in gastric GIST were: female gender (HR 0.60; 95%CI 0.37-0.97) and KIT ex 11 point mutations (HR 0.22; 0.70-0.73), while in non-gastric GIST: KIT ex 11 codon 557-558 deletions (HR 0.43; 0.24-0.75), point mutations (HR 0.48; 0.27-0.87) or other KIT ex 11 alterations (HR 0.40; 0.23-0.70) and no PDGFRA ex 18 D842V mutation (HR 0.11; 0.04-0.34). Only factors associated with OS in gastric GIST were: female gender (HR 0.41; 95%CI 0.24-0.70) and no PDGFRA ex 18 D842V mutation (HR 0.32; 0.14-0.71), while KIT ex 11 other deletions/indels/duplications (HR 0.57; 0.36-0.88) in non-gastric GIST. Table: 1513P
Distribution of mutational aberrations in advanced GIST patients
| Overall (n=344) % | Gastric (n=123) % | Non-gastric (n=221) % | p | |
| KIT exon 11 wild-type | 32.0 | 33.3 | 31.2 | 0.003 |
| KIT exon 11 codons 557-558 deletion | 29.7 | 39.8 | 24 | |
| KIT exon 11 other deletions, duplications, indels, | 23.5 | 17.1 | 27.1 | |
| KIT exon 11 point mutations | 14.8 | 9.8 | 17.6 | |
| KIT exon 9 wild-type | 87.2 | 98.4 | 81.0 | <0.001 |
| KIT exon 9 codons 502-502 duplication | 12.8 | 1.6 | 19.0 | |
| KIT mutations other than exon 9 and 11 | 1.2 | 0.8 | 1.4 | - |
| PDGFRA exon 18 wild-type | 95.3 | 90.2 | 98.3 | <0.001 |
| PDGFRA exon 18 D842V mutation | 3.5 | 6.5 | 1.8 | |
| PDGFRA exon 18 codons 842-847 indels | 1.2 | 3.3 | 0 | |
| PDGFRA mutations other than exon 18 | 0.3 | 0.8 | 0 | - |
Conclusions
Mutational status of KIT and PDGFRA genes impact the long-term efficacy of imatinib in different cohorts of GIST and can serve as prognostic and predictive factor.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Sobczuk: Financial Interests, Personal, Other, Travel grant: Novartis; Financial Interests, Personal, Other, Travel Grant: MSD, Pierre Fabre, BMS; Financial Interests, Personal, Invited Speaker: Swixx BioPharma, BMS, Gilead; Financial Interests, Personal, Stocks/Shares: CelonPharma; Non-Financial Interests, , Leadership Role, Board Member, Chair of Young Oncologists Section: Polish Society of Clinical Oncology. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, , Officer: ASCO; Non-Financial Interests, Invited Speaker, President Elect: Polish Oncological Society. All other authors have declared no conflicts of interest.