Early outcomes of exon 11 mutants in GIST treated with standard dose Imatinib.

Background: The exon 11 KIT mutant gastrointestinal stromal tumors (GIST) is a heterogeneous cohort with variable biological behavior based on different mutational subtypes.

Methods: Patients with histologically proven GIST with KIT exon 11 mutations were selected from a prospectively maintained database, and evaluated for clinical characteristics and event free survival (EFS). Patients were divided into mutations upstream to codon 557 (G1), mutations involving codon 557-558 (G2) and mutation downstream to codon 558 (G3).

Results: A total of 90 patients satisfied the inclusion criteria for study. Substitutions, indels and duplications were seen in 23 patients. Deletions were seen in 67 patients, of which 44 patients had large deletions (>6 base pairs), while 23 has small deletions (<6 base pairs). Complex mutations were seen in 15 patients. G2 mutations were noted in 33 patients, while G1 and G3 mutations were seen 32 and 25 patients respectively. With a median follow-up of 26 months, estimated median EFS for the entire cohort was 55 months. The G2 cohort had an inferior EFS compared to the G1 and G3 cohorts (46 55 months), but this did not achieve statistical significance (univariate analysis: P=0.075). On multivariate analysis, patients undergoing radical intent surgery no surgery (58 55 months; P=0.005) and G1 or G3 G2 cohort (P=0.058) showed trend towards improved EFS.

Conclusions: In patients with GIST exon 11 codon 557-558 mutation subset there is a trend towards an inferior survival even when treated with imatinib mesylate (IM).