(P 113) PROGNOSTIC AND/OR PREDICTIVE VALUE OF EXON 11 MUTATIONS IN TUMOR RESPONSE TO IMATINIB IN METASTATIC GASTROINTESTINAL STROMAL TUMOR :RETROSPECTIVE ANALYSIS OF A MULTICENTRIC NATIONAL REGISTRY

Objective: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignant neoplasm of the gastrointestinal tract. The majority of GISTs are driven by gain-of-function mutations in KIT which exhibits a predictive role for TKI sensibility. Thus, patients harboring exon 11 mutations are the most sensitive to imatinib. Additionally, patients carrying exon 11 mutations that involves 557 and/or 558 codons (from now on we will refer it as critical mutation, CM,) had significantly shorter relapse free survival.
The objective of this retrospective analysis is to evaluate the prognostic/predictive role of exon 11 mutations, comparing CM with other mutations affecting other codons of exon 11, in the outcome of the disease and the response to imatinib at first line

Methods: Patient with metastatic exon 11 mutated GIST, treated at first line with imatinib were retrospectively selected from the GEIS sarcoma Registry. Two cohorts were stablished according to CM or other mutations in other location within exon 11.
Demographics, clinical data, treatment characteristic and outcome in the two different cohorts was collected. Progression free survival (PFS) to imatinib and overall survival (OS) were analyzed by Kaplan-Meier, significance was calculated by log-rank test.

Results: 216 patients were analyzed, of which 43 harbored CM and 173 presented other mutations. Median age was 58y in CM and 59y in patients with other mutations in exon 11.
In both groups, patients were predominantly men, half of them had over 10 mitosis and size over 10cm. The primary tumor location was predominantly gastric followed by small bowel in all goups. Metastatic tumors at diagnostic time was seen in 50% in the subset of “other mutations” while it occurred in 33% in the CM subgroup..
The median of PFS was 28 month (19-37) in CM group vs 25 m (21-29) in the group with other mutation in exon 11 p=0,048. Mutation status did not correlate with OS [CM 67 month (28-106m) vs others mutation 79m (56-102m) p=0,186]. Deletion-type mutations in exon 11 were associated with shorter PFS independently of the position: [71m (35-106) vs 79m (57-110m) p= 0,04]

Conclusion: In this preliminary and exploratory analysis, patients harboring CM showed longer PFS to imatinib in the first line therapy of advanced disease than patients with other mutations within exon 11.