P-132 Molecular profiling of KIT and PDGFRA in Chilean GIST patients: A Latin-American perspective

Background: While rare, localized, resectable GI stromal tumors (GIST) are usually associated with high survival. On the other hand, non‐resectable or advanced stage GISTs display a good response to tyrosine kinase inhibitors (TKI) such as imatinib or sunitinib. Current guidelines recommend mutational profiling of these patients for an optimal management. This can be performed either at diagnosis or after recurrence, searching for specific gene alterations on KIT or PDGFRA to determine the best therapeutical approach. Here, we report the mutational profile of 54 Chilean GIST patients. We also include clinical and pathological features, and the TKI recommendation based on exon‐specific mutational analyses. Methods: A total of 54 patients were included in our study. They are part of our ongoing GIST registry. In this subset, we analyzed clinical and pathological data, and genomic alterations in KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12, 14, and 18). We evaluated the frequency of various KIT/PDGFRA alterations and potential treatment recommendations. Results: Median age at diagnosis in this subset was 53 years (IQR: 19.3). Most patients were female (29/54; 53.7%). As expected, the most frequent primary site was the stomach (27 cases, 50.0%), followed by small intestine (21 cases, 38.9%). The mitotic rate was predominantly high (>5) in 22/54 patients (40.7%). 17 patients (31.5%) presented metastatic disease at diagnosis. The modified NIH risk of recurrence was assessed in 30 patients with localized GIST at diagnosis, with an intermediate risk in 9 (30.0%) and a high risk of recurrence in 21 patients (70.0%). All patients received adjuvant imatinib. 32 patients (59.3%) had KIT mutations. Exon‐11 was the most frequently altered (28 cases, 51.9%) followed by exon‐9 (4 cases, 7.4%). On the other hand, PDGFRA mutations were found in 23 patients (42.6%). 5 patients (9.3%) had pathogenic alterations such as D842V on exon‐18. Interestingly, from the remaining 18 patients (33.3%), 10 (18.5%) had silent alterations in the PDGFRA gene, such as exon‐12 P567P and exon‐18 V824V, allowing clinical management of these patients as PDGFRA wild‐type (WT). The remaining eight patients (14.8%) had KIT‐PDGFRA WT GISTs, which added to the patients with PDGFRA silent alterations result in 18 patients (33.3%) where a WT GIST clinical approach could be used. Based on our findings, first‐line imatinib or sunitinib was recommended in 36 (66.7%) or 18 (33.3%) patients, respectively. Four patients (7.4%) harbored alterations associated with both imatinib and sunitinib treatment resistance. Finally, the frequency of grade 2 or 3 toxicities was 28.6% (12 cases) in patients receiving imatinib in first‐line, with grade 3 cutaneous rash and heart failure as the most clinically relevant toxicities. Conclusions: To our knowledge, this is the first report of a mutational profile in GIST patients in a Latin American population. Notably, 33.3% of our patients required a WT clinical approach even after the mutational analysis, increasing the use of first‐line sunitinib. Future NGS studies on WT GISTs could reveal novel molecular alterations. Legal entity responsible for the study: The authors. Funding: Donation from Fundación GIST Chile. Disclosure: All authors have declared no conflicts of interest.