ESMO Congress 2023 | OncologyPRO

Abstract 1977P

Background

Gastrointestinal stromal tumors (GIST) are characterized by multiple subtypes with distinct biological features. Here, we report the frequency of classified mutations and the projected frequency of unclassified KIT/PDGFRA Wildtype (KIT/PDGFRA WT) mutations in GIST patients that received mutational testing.

Methods

This data was supplied by the Life Raft Group (LRG) Registry. Of 2465 patients, 55.3% (n=1363) had mutational testing (Tested) and 44.7% (n=1102) did not (Untested). We used the distribution of classified KIT/PDGFRA WT that had further testing to estimate the frequency in unclassified KIT/PDGFRA WT. By assuming the distribution of unclassified Wildtype patients is similar to the classified patients, we projected the entire cohort by multiplying the percentage of each classified KIT/PDGFRA WT mutation to the total number of unclassified KIT/PDGFRA WT patients (n=101).

Results

Tested Patients Out of 1363 Tested patients, the distribution was: KIT 77.8% (n= 1060), PDGFRA 7.6% (n= 104), SDHx 4.8% (n= 66), NF1 1.5% (n= 20), BRAF (includes 1 fusion) 0.6% (n= 8), ETV6-NTRK3 fusion 0.2% (n= 2), PTCH1 0.1%(n=1), NTRK 0.1%(n=1). KIT/PDGFRA WT Approximately half (49.2%, n= 98) of KIT/PDGFRA WT patients had further testing (classified), e.g., SDHx, NF1, BRAF, etc. The other half (50.8%, n=101) had no further or inconclusive testing (unclassified), which are recorded as “Wildtype” (WT) in the registry. Table displays the projected number of patients in unclassified WT and the overall projection of all Tested patients. Table: 1977P

Known and projected mutation distribution

Gene	Tested Patients (Known) n=(%)	Classified WT KIT/PDGFRA Mutation Rate % (n=98)	Projected No of Patients in Unclassified WT (n=101)	Known & Projected Patients	Projected Rate (%)
Kit	1060 (77.8%)	NA	NA	1060	77.8%
PDGFRA	104 (7.6%)	NA	NA	104	7.6%
Unclassified WT	101 (7.4%)	NA	-	NA	NA
SDHA	31 (2.3%)	31.6	32	63	4.6%
SDHB	21 (1.5%)	21.4	22	43	3.2%
NF1	20 (1.5%)	20.4	21	41	3.0%
SDHC	9 (0.7%)	9.2	9	18	1.3%
BRAF	7 (0.5%)	7.1	7	14	1.0%
SDH-C Epimutant	4 (0.3%)	4.1	4	8	0.6%
ETV6-NTRK3 Fusion	2 (0.1%)	2.0	2	4	0.3%
AGAP3-BRAF Fusion	1 (0.1%)	1.0	1	2	0.1%
SDHD	1 (0.1%)	1.0	1	2	0.1%
NTRK	1 (0.1%)	1.0	1	2	0.1%
PTCH1	1 (0.1%)	1.0	1	2	0.1%
Total	1363 (100%)	100%	101	1363	100%

Conclusions

By using the methods described, we were able to project the frequency of mutations in LRG registry patients and identified a higher frequency of unclassified mutations. A well-defined mutation can provide important information to optimize clinical decision-making, including diagnosis, prognosis, treatment selection, and monitoring treatment response.