KIT and PDGFRA Variants and the Survival of Patients with Gastrointestinal Stromal Tumor Treated with Adjuvant Imatinib

Abstract

Adjuvant imatinib improves the recurrence-free survival and overall survival (OS) of patients with gastrointestinal stromal tumors (GISTs) who have a high risk of recurrence after surgery and is now considered standard treatment. Yet, OS benefit has been demonstrated in only one randomized study, the Scandinavian Sarcoma Group XVIII/AIO trial, where patients with high-risk GISTs were allocated to either 1 year or 3 years of adjuvant imatinib. SSGXVIII/AIO is also the only randomized trial in which adjuvant imatinib duration exceeding 2 years was evaluated. In this trial, the 3-year treatment led to a 45% reduction in the risk of death during the first 10 years that followed random allocation even though some of the patients did not have GISTs at tumor histology review, had mutations now known to be imatinib-resistant or had non-localized disease at study entry. In the subgroup of patients who had KIT exon 11 deletion/indel mutation, the reduction in the risk of death was 66% in favor of the longer treatment. Proper patient selection is of crucial importance since many patients are cured with surgery. Little evidence for OS benefit is available from randomized trials for patients whose GIST harbors KIT exon 9 mutation, KIT insertion mutation, PDGFRA D842V mutation, or lacks KIT and PDGFRA mutations. Adjuvant imatinib improves OS substantially if high-risk GISTs can be identified, treatment duration is long enough, and GISTs harbor an imatinib-sensitive mutation.

Clinicopathological Characteristics and the First Mutational Analysis of Gastrointestinal Stromal Tumors From Mexico: A Single Institution Experience

“…In general, the mutation in exon 11 was associated with a favorable recurrence-free survival and in exon 9 unfavorable. In our study, due to the sample size, reliable data cannot be obtained regarding the association of exon mutation and disease-free period; however, it is important to mention that of the total of patients who developed recurrence, four cases were of high risk according to mitotic index, all developed metastases, 100% were positive for CD117 and DOG1 and negative for CD34, three cases had KIT mutations, where two were in exon 11 and one in exon 9, with position 576, 554, and 502, respectively [ 22 , 29 ].…”

The Role of Neoadjuvant Therapy in a Giant Gastric Gastrointestinal Stromal Tumour: A Case Report and Review of the Literature

“…Furthermore, imatinib has been shown to be beneficial as adjuvant treatment in randomized clinical trials for patients with a high risk of recurrence [8][9][10]. This drug improves the overall survival and recurrence-free survival of patients with GIST who have a high risk of relapse after surgery and is now considered the standard treatment [11]. It is anticipated that neoadjuvant therapy with imatinib will cause a notable decrease in tumour size, which might enhance the complete resection rate, prevent the need for multi-organ resection, and lower the risk of surgery.…”