Abstract 63P
Background
KIT/PDGFR wild-type (KPWT) gastrointestinal stromal tumors (GIST) constitute a minority of all metastatic GIST cases. Most studies to date involve case reports or small series, and treatment approaches vary widely among teams. Additional research is needed to define the optimal management of metastatic KPWT GIST patients. This retrospective study aimed to assess the outcomes of KPWT GIST patients treated with Tyrosine Kinase Inhibitors (TKI) at our institution.
Methods
We conducted a retrospective study at the Centre Léon Bérard (CLB). The NetSarc national sarcoma database was queried for KPWT GIST patients at CLB. Data were extracted from individual patient files and reviewed by an expert sarcoma pathologist. Whole exome-RNAseq was performed with FFPE material in the absence of known neurofibromatosis type 1 (NF1) or SDH-deficiency.
Results
A total of 78 KPWT GIST patients were identified. Four molecular groups could be formed, NF1-associated GIST (N=29), SDHB-deficient GIST (N=13), other rare alterations (N=7 with 3 BRAF V600E mutation, 1 NTRK3 rearrangement, 1 TSC1 variant, 1 FLNA mutation, and 1 FGFR2 mutation), and wild-type GIST (N=29). SDHB-deficient GIST patients were significantly younger (p-value = 0.0006), and NF1-associated GIST were more likely to be primarily located in the small intestine (p-value < 0.0001). Median PFS with imatinib was 9.5 months (with a noteworthy PFS of 199 months in a wild-type GIST), and 10 months with sunitinib. Regorafenib was significantly less effective with a median PFS of 3 months (p-value = 0.01). Pazopanib showed the highest median PFS of 30 months (with a notable PFS of 116 months in an SDHB-deficient GIST). Overall survival was of 190 months for NF1-patients, 246 months for SDHB-patients, 45.7 months with other molecular alterations, and 185 months for wild-type GIST (p-value = 0.5).
Conclusions
This retrospective series is one of the largest describing clinical characteristics and treatment response of KPWT GIST, a rare disease. Imatinib and sunitinib demonstrated good responses, while regorafenib showed no efficacy. Long responders were reported with multi-targeted TKI, warranting further investigation through prospective trials to validate those results.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
M. Dupont.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.